负重训练和补充大豆多肽干预大鼠骨骼肌衰老效果及机制研究
|
摘要
随着全世界老龄化国家增多,老龄人口比率加大,人口的老龄化已经成为许多国家都要面对的新的突出的社会问题。如何延长老年人的健康寿命,提高生活质量已成为各国政府和社会各界关注的焦点。对衰老和衰老相关疾病的研究历来就是世界性的医学课题,探索衰老的本质,寻找有效的抗衰老药物和方法,以求得预防衰老过早出现和延缓衰老的进程已成为当前老年医学领域中的研究热点。近年来,老年人骨骼肌功能的衰退受到了科研人员的重视,因为人们发现骨骼肌的衰老会加速人体整体的衰老进程,而骨骼肌功能的恢复对提高老年人的健康水平和生活质量都十分有意义。
目前对于预防和延缓衰老主要集中在药物研究上,尽管药物干预有一定的临床效果,但是同时又存在着作用局限、有毒副作用等不足。运动是生命活动的基础,而营养则是生命活动直接的保障,如何将运动和营养干预这两种更为经济和安全的方式结合起来,使身体各器管、各系统的功能产生良好的效应,以对抗机体衰老,特别是骨骼肌的衰老,值得深入研究和探讨。
针对运动干预衰老的研究,国内外已有相关的报道,但多数研究是对人体整体机能的调节和影响,指标也较为单一,缺少针对某一器官和组织,尤其是缺少运动抗骨骼肌衰老的机理及综合指标的研究,选择形式也以有氧运动或短期力量训练为主,对骨骼肌刺激更明显的长期抗阻力量训练或负重训练的研究较少,作用效果也不明确。国内外针对营养干预衰老的研究也较多,相关的营养补剂产品也层出不穷,但从整体、组织、基因不同层面入手,观察长期补充大豆天然提取物大豆多肽对骨骼肌衰老的影响并探讨其机制,国内外还没有见到相关文献的报道。
本研究就是运用衰老研究中常用的D-半乳糖皮下注射的方法,复制大鼠亚急性骨骼肌衰老模型,并在造模过程中和造模成功后都进行负重训练和补充大豆多肽的干预。通过观察一般指标、骨骼肌组织切片和相应的生化指标,判定两种干预方式对预防骨骼肌衰老过早出现和延缓骨骼肌衰老的作用效果,同时测量血清及骨骼肌超氧化物歧化酶(SOD)和丙二醛(MDA)、血清睾酮(T)、皮质醇(C)、生长激素(GH)和胰岛素样生长因子- I (IGF-I)、骨骼肌总蛋白和脂褐素、骨骼肌肌动蛋白(α-actin)、IGF-I和生长分化因子-8(GDF-8)mRNA等指标,初步探讨两种干预方式在预防和延缓骨骼肌衰老中的作用机制,为进一步进行人群干预试验积累一定的理论和实验基础,为提供更有针对性的运动方式和研制、开发合理有效的营养补剂,以对抗中老年人骨骼肌的衰老,开辟一条新思路和新途径。同时,也为指导中老年人科学的健身,合理进行慢性病的康复,提高健康水平和生活质量,提供一定的帮助和借鉴。
实验分为两部分:预防衰老实验和延缓衰老进程实验
一、预防衰老实验
3月龄SD雄性大鼠56只,随机分为7组:成年组(C)、D-半乳糖组(M)、D-半乳糖小负重组(S)、D-半乳糖大负重组(B)、D-半乳糖补肽组(P)、D-半乳糖补肽小负重组(PS)、D-半乳糖补肽大负重组(PB)。所有大鼠在6周D-半乳糖造模的过程中进行相应的负重训练和补充大豆多肽的干预。6周末处死,比较各组一般指标、骨骼肌组织切片、血清和骨骼肌组织生化以及分子生物学指标,结果如下:
1.一般指标:所有造模组大鼠均出现了衰老的外观特征,体重呈现自然增长趋势,双侧腓肠肌总重量、腓肠肌相对重量有下降的趋势,各干预组大鼠以上变化幅度趋缓;所有组大鼠每日摄食量都有下降的趋势,造模组趋势更为明显。提示:两种干预方式可以有效改善衰老的外部特征。
2.骨骼肌组织切片:光镜下观察C组大鼠为正常骨骼肌组织学特征,所有造模组大鼠均出现不同程度的肌细胞萎缩或退行性改变特征,以M组变化最为明显。提示:两种干预方式可以有效预防骨骼肌衰老过早的出现。
3.血清学指标:与C组相比,M组大鼠血清中SOD活力及SOD/MDA、T含量及T/C、GH含量显著下降,血清MDA含量、C含量显著上升,(P<0.01或P<0.05)血清IGF-I含量有下降的趋势,但无显著性差异;负重训练或补充大豆多肽干预可以有效的逆转以上趋势,均以小负重组表现更为明显,并且两种干预方式均具有显著的交互作用。提示:两种干预方式可以减轻D-半乳糖造成的机体脂质过氧化和激素水平的紊乱。
4.骨骼肌组织生化指标:与C组相比,M组大鼠骨骼肌SOD活力、MDA含量、脂褐素含量显著升高(P<0.01或P<0.05),SOD/MDA有降低的趋势,但无显著性差异;骨骼肌总蛋白含量显著下降(P<0.05);负重训练或补充大豆多肽干预除可以进一步提高骨骼肌SOD活力外,均可以逆转其他的趋势,多数以小负重组表现更为明显,并且以上情况两种干预方式均具有显著的交互作用。提示:两种干预方式可以减轻D-半乳糖造成的骨骼肌组织脂质过氧化和肌蛋白合成的减少。
5.骨骼肌组织分子生物学指标:与C组相比,M组大鼠骨骼肌组织中α-actin mRNA和IGF-I mRNA表达显著下降(P<0.01);GDF-8 mRNA表达显著升高(P<0.01);负重训练或补充大豆多肽干预可以有效的逆转以上的趋势,均以小负重组表现更为明显,并且两种干预方式均具有显著的交互作用。提示:两种干预方式可以升高D-半乳糖造成的骨骼肌组织α-actin mRNA和IGF-I mRNA的低表达,降低GDF-8 mRNA的高表达。
二、延缓衰老进程实验
3月龄SD雄性大鼠60只,随机分为8组:6周安静对照组(C6)、6周模型组(M6)、12周模型组(M12)、造模后大负重组(B12)、造模后小负重组(S12)、造模后补肽组(P12)、造模后补肽大负重组(PB12)、造模后补肽小负重组(PS12),14月龄SD雄性大鼠8只作为自然衰老组(OC)。除C6组、M6组、M12组和OC组,其余各组在6周D-半乳糖造模后进行相应的负重训练和补充大豆多肽的干预。分别于6周末和12周末处死相应组大鼠,测试相关指标,结果如下:
1. 6周组指标比较:与C6相比,M6组大鼠体重升高,腓肠肌总重量及相对重量均有降低的趋势,但均未达到统计学差异;血清SOD活力显著降低(P<0.05),血清MDA和骨骼肌脂褐素含量均显著升高(P<0.01);骨骼肌切片均出现不同程度的肌细胞萎缩或退行性改变特征。提示:造模成功。
2. 12周一般指标:所有造模组和OC组大鼠均出现了衰老的外观特征,各干预组大鼠衰老特征较轻;所有组大鼠体重呈现自然增长趋势,各干预组大鼠其幅度明显趋缓(P<0.05),两种干预方式具有显著的交互作用;两种干预方式使双侧腓肠肌总重量显著降低(P<0.05和P<0.01),有显著的交互作用,腓肠肌相对重量有降低的趋势,无显著的交互作用;各组大鼠每日摄食量呈现平稳增长的趋势,两种干预方式使增长幅度趋缓,无显著的交互作用。提示:造模成功后,再进行两种方式的干预,可以有效延缓衰老进程中的外部特征。
3. 12周骨骼肌组织切片:光镜下观察各组大鼠肌细胞形态有着不同程度的萎缩或退行性改变,以M12组和OC组变化最为明显,提示:造模成功后,再进行两种方式的干预,可以有效延缓骨骼肌衰老的进程。
4. 12周血清学指标:与OC组相比,M12组大鼠血清SOD活力、MDA含量以及SOD/MDA、血清T含量、C含量以及T/C、血清GH和IGF-I含量均无显著性差异。负重训练或补充大豆多肽可以显著提高血清SOD活力以及SOD/MDA、T含量以及T/C、GH和IGF-I含量,降低血清MDA含量和C含量,多数以小负重组表现更为明显,并且两种干预方式都具有显著的交互作用。(P<0.05或P<0.01)提示:造模成功后,再进行两种方式的干预,可以减轻机体脂质过氧化和激素水平的紊乱。
5. 12周骨骼肌组织生化指标:与OC组相比,M12组大鼠骨骼肌SOD活力、MDA含量及SOD/MDA、总蛋白含量和脂褐素含量均无显著性差异。负重训练或补充大豆多肽可以显著提高骨骼肌SOD活力及SOD/MDA、总蛋白含量,降低骨骼肌MDA含量和脂褐素含量,多数以小负重组表现更为明显,并且两种干预方式都具有显著的交互作用。(P<0.05或P<0.01)提示:造模成功后,再进行两种方式的干预,可以减轻骨骼肌组织脂质过氧化和肌蛋白合成的减少。
6. 12周骨骼肌组织分子生物学指标:与OC组相比,M12组大鼠骨骼肌α-actin mRNA、IGF-I mRNA和GDF-8 mRNA表达均无显著性差异。负重训练或补充大豆多肽干预可以提高骨骼肌α-actin mRNA和IGF-I mRNA的表达,降低GDF-8 mRNA的表达,均以小负重组表现更为明显,并且两种干预方式都具有显著的交互作用。(P<0.05或P<0.01)提示:造模成功后,再进行两种方式的干预,可以升高骨骼肌组织α-actin mRNA和IGF-I mRNA的低表达,降低GDF-8 mRNA的高表达。
结论
1. 6周D-半乳糖皮下注射,可以成功复制大鼠亚急性骨骼肌衰老模型。可能的作用机制为:①增多血液中自由基;②增强骨骼肌氧化应激以及脂质过氧化;③增加骨骼肌脂褐素的沉积;④促使激素及相关因子的代谢紊乱;⑤降低骨骼肌α-actin和IGF-I mRNA的表达,提高骨骼肌GDF-8 mRNA的表达。
2.负重训练或补充大豆多肽均可以有效的预防6周D-半乳糖造模过程中大鼠骨骼肌衰老过早的出现,以小负重训练效果最好,而且两种方式联合运用效果更为明显。
3. 6周负重训练或补充大豆多肽的干预均可以对6周D-半乳糖造模后大鼠骨骼肌衰老有积极的延缓作用,以小负重训练效果最好,而且两种方式联合运用效果更为明显。
4.负重训练和补充大豆多肽预防和延缓大鼠骨骼肌衰老的效果可能通过下列机制发挥作用:①减少血液中自由基;②减轻骨骼肌氧化应激以及脂质过氧化;③减少骨骼肌脂褐素的沉积;④纠正激素及相关因子的代谢紊乱;⑤提高骨骼肌α-actin和IGF-I mRNA的表达,降低骨骼肌GDF-8 mRNA的表达。
With the increasing of the world aging country and the proportion of old people, many countries face with the new and projecting problem of aging population. The governments and societies focus on how to improve people’s healthy life-span and life quality. The research in senescence and its correlated disease has been taking the worldwide medical subject invariably. At present, explore the essential of aging, search the effective antiaging agents and methods to prevent and postpone aging have become the hotspot study in the area of geriatric medicine. Recent years, the scientists pay more attention to the issue of decline of muscle function, because it can influence old people’s health. It is close correlative between the muscle function and senescence.
At present, most research about preventing and postponing aging focus on drugs. Although drugs have certain effect, their disadvantages of limitation and side effect are also obvious. Exercise is the basis of vital movement, and nutrition is the immediate guarantee of it. How to combine the exercise and nutrition together in an economic and safe way, make the organs and systems in a satisfactory condition, in order to confront the aging especially the muscle aging , it is worth to be studied thoroughly.
There are some correlative reports of exercise interference in aging. Although, most research are about the influence of whole function, the parameteres are limited and lack of the study in certain organ and tissue ,especially be short of the research in mechanism and comprehensive parameter of exercise interference in aging. Also, the exercise styles are in aerobic and short term strength training mostly, the patterns in long term strength and weight training which are more effective to the skeletal muscle are less, the affect are indefinite either. There are many studies of nutrition interference in aging in and out doors, the relative nutritional supplements are also to come out one after the other. Though, there is no correlated reports about the mechanism and effect of the long term soy polypeptide supplement in skeletal muscle aging from the aspects of whole body, tissue and genes.
The present research copys the rat subacute skeletal muscle aging model by the method of D-galactose hypodermic which is common in senescence study. And take the interference way in weight training and soy polypeptide supplement in and after the process of model making. The research aims to observe the general parameter, skeletal muscle tissue slice and biochemical parameter, in order to judge the prevention and postpone effect in skeletal muscle aging by the two interference ways. and to discuss the probable mechanisms by measuring serum & skeletal muscle superoxide dismutase (SOD) and malondealdehyde (MDA), serum testosterone(T), cortisol(C), growth hormone(GH) and insulin-like growth factor-1(IGF-I), skeletal muscle total protein level and lipofuscin, skeletal muscleα-actin,IGF-I and growth and differential factor-8(GDF-8) mRNA. With the purpose of accumulating the theory and experiment foundation in further human test, opening a new thinking and way to be against skeletal muscle aging in middle-old aged people by providing more direct exercise way and developing effective nutritional supplement. At the same time, it can provide some help of middle-old aged people in the direction of scientific body building, the reasonable recovery from chronic disease and the elevation of health level and quality of life.
The experiment is consisted of two parts, prevention aging part and delaying senility part.
Part I Prevention aging experiment
Fifty-six three month male Sprague-Dawley (SD) rats were randomly assigned into seven groups: adult group (C), D-galactose group (M), D-galactose small load exercise group(S), D-galactose big load exercise group (B), D-galactose peptide group (P), D-galactose peptide and small load exercise group(PS), D-galactose peptide and big load exercise group (PB). All the rats were taken the interference way in weight training and soy polypeptide supplement in the process of 6w D-galactose hypodermic. By the end of 6th week, all rats were killed and serum and skeletal muscle parameters were evaluated.
1. General parameter: All the model rats showed up the aging appearances, the body weight were in normal increase trend, di-gastrocnemius &relative weight were in the decrease trend ,and all the rats in interference group could slow down the above trend; All the rats quotidie ingestion were in the decrease trend, the model groups were in obvious way. Results indicate that two interference way can improve the aging appearances effectively.
2. Skeletal muscle tissue slice: Under light microscope, the rats in group C were in normal skeletal muscle histologic characteristics, All the model rats showeg up muscle cell atrophy or regressive changes in a different level, especially the rats in group M. Results indicate that two interference way can prevent the premature appearance in skeletal muscle aging.
3. Serum parameter: Compare with group C, the serum SOD, SOD/MDA, T, T/C and GH in group M were lower, MDA and C were higher.(significant or very significant difference, P<0.05 or P<0.01), but serum IGF-I was in decrease trend and had no statistic difference; Weight training or soy polypeptide supplement could reverse the trend, the groups of small load all had more obvious appearance, and they had notable interaction. Results indicate that two interference way can alleviate organism lipid peroxidation and hormone abnormality due to D-galactose.
4. Skeletal muscle biochemical parameter: Compare with group C, the skeletal muscle SOD, MDA and Lipofuscin in group M were higher (significant or very significant difference, P<0.05 or P<0.01), but SOD/MDA was in decrease trend and had no statistic difference (P>0.05), skeletal muscle total protein level was lower(significant difference, P<0.05); Weight training or soy polypeptide supplement could make skeletal muscle SOD in a further increase and reverse the rest trend, the groups of small load had more obvious appearance in majority, also they had notable interaction. Results indicate that two interference way can alleviate skeletal muscle lipid peroxidation and low myoprotein synthesis due to D-galactose.
5. Skeletal muscle molecular biological parameter:Compare with group C, the skeletal muscleα-actin mRNA and IGF-I mRNA in group M were lower,but GDF-8 mRNA was higher(very significant difference, P< 0.01); Weight training or soy polypeptide supplement could reverse the trend, the groups of small load all had more obvious appearance, and they had notable interaction. Results indicate that two interference way can increase the low expression ofα-actin mRNA and IGF-I mRNA and decrease the high of GDF-8 mRNA due to D-galactose.
Part II Delaying senility experiment
Sixty three month male SD rats were randomly assigned into eight groups: 6w control group (C6), 6w model group (M6), 12w model group (M12), small load exercise group(S12), big load exercise group (B12), peptide group (P12), peptide and big load exercise group (PB12),peptide and small load exercise group(PS12)), eight fourteen month male SD rats were taken the natural aging group(OC). Besides the group C6, M6, M12 and OC, all the other rats were taken the interference way in weight training and soy polypeptide supplement after 6w D-galactose hypodermic. By the end of 6th week and 12th week, the corresponding rats were killed and serum and skeletal muscle parameters are evaluated.
1.Comparison between group C6 and M6: Compare with group C6, the di-gastrocnemius &relative weight in group M6 were in the decrease trend, though they had no statistic difference; the serum SOD in group M6 was lower (significant difference, P<0.05), serum MDA and skeletal muscle lipofuscin were higher (very significant difference P<0.01), All the skeletal muscle tissue slices showed up muscle cell atrophy or regressive changes in a different level. These results indicate that the skeletal muscle aging model is successful.
2. General parameter of 12 week: All the model rats and group OC showed up the aging appearances, the rats in interference group could slow down the above trend; The body weight in all groups were in normal increase trend, the rats in interference group could slow down it obviously(significant difference, P<0.05),and two interference way had notable interaction; two interference way could make di-gastrocnemius &relative weight in the decrease trend(significant or very significant difference, P<0.05 or P<0.01), and maked it relative weight in a decrease trend; All the rats quotidie ingestion were in the increase trend, two interference way could make it in a reverse way, but had no notable interaction .Results indicate that two interference way can improve the aging appearances effectively after the process of model.
3. Skeletal muscle tissue slice of 12 week: Under light microscope, All the model rats showed up muscle cell atrophy or regressive changes in a different level, especially the rats in group M12 and OC. Results indicate that two interference way can postpone the course in skeletal muscle aging after the process of model.
4.Serum parameter of 12 week: Compare with group OC, the serum SOD, MDA, SOD/MDA, T, C, T/C, GH and IGF-I in group M12 had no statistic difference. Weight training or soy polypeptide supplement could increase the content of serum SOD, SOD/MDA, T, T/C, GH and IGF-I, decreased the content of serum MDA and C, the groups of small load had more obvious appearance in majority, and they had notable interaction. (significant or very significant difference, P<0.05 or P<0.01).Results indicate that two interference way can alleviate organism lipid peroxidation and hormone abnormality after the process of model.
5. Skeletal muscle biochemical parameter of 12 week: Compare with group OC, the skeletal muscle SOD, MDA, SOD/MDA, total protein level and lipofuscin in group M12 had no statistic difference. Weight training or soy polypeptide supplement could increase the content of skeletal muscle SOD, SOD/MDA and total protein level, decreased the content of skeletal muscle MDA and lipofuscin, the groups of small load had more obvious appearance in majority, and they had notable interaction. (significant or very significant difference, P<0.05 or P<0.01). Results indicate that two interference way can alleviate skeletal muscle lipid peroxidation and low myoprotein synthesis after the process of model.
6. Skeletal muscle molecular biological parameter of 12 week:Compare with group OC, the skeletal muscleα-actin mRNA and IGF-I mRNA in group M12 had no statistic difference. Weight training or soy polypeptide supplement could increase the expression ofα-actin mRNA and IGF-I mRNA, decreased the expression of GDF-8 mRNA, the groups of small load all had more obvious appearance, and they had notable interaction. Results indicate that two interference way can increase the low expression ofα-actin mRNA and IGF-I mRNA , decrease the high of GDF-8 mRNA after the process of model.
Conclusions
1. Rat skeletal muscle aging model can be copied successfully by 6 week D-galactose hypodermic and the probable pathogenesy are as follows:①increase the blood free radical;②increase skeletal muscle oxidative stress and lipid peroxidation;③increase the deposition of lipofuscin in skeletal muscle;④promote the metabolic disorder of hormone and correlation factors;⑤decrease the expression of skeletal muscleα-actin mRNA and IGF-I mRNA, increase the expression of skeletal muscle GDF-8 mRNA.
2. Weight training or soy polypeptide supplement can prevent the premature appearance in skeletal muscle aging resulted from 6 week D-galactose model effectively, the exercise of small load has the best result, and the two interference way united can have more obvious effect.
3. 6 week weight training or soy polypeptide supplement can have an active postpone effect of skeletal muscle aging after the 6 week D-galactose model, the exercise of small load has the best result, and the two interference way united can have more obvious effect.
4. The mechanisms of preventive and postponed effect of weight training and soy polypeptide supplement in skeletal muscle aging are probably as follows:①decrease the blood free radical;②decrease skeletal muscle oxidative stress and lipid peroxidation;③decrease the deposition of lipofuscin in skeletal muscle;④correct the metabolic disorder of hormone and correlation factors;⑤i ncrease the expression of skeletal muscleα-actin mRNA and IGF-I mRNA, decrease the expression of skeletal muscle GDF-8 mRNA.
目前对于预防和延缓衰老主要集中在药物研究上,尽管药物干预有一定的临床效果,但是同时又存在着作用局限、有毒副作用等不足。运动是生命活动的基础,而营养则是生命活动直接的保障,如何将运动和营养干预这两种更为经济和安全的方式结合起来,使身体各器管、各系统的功能产生良好的效应,以对抗机体衰老,特别是骨骼肌的衰老,值得深入研究和探讨。
针对运动干预衰老的研究,国内外已有相关的报道,但多数研究是对人体整体机能的调节和影响,指标也较为单一,缺少针对某一器官和组织,尤其是缺少运动抗骨骼肌衰老的机理及综合指标的研究,选择形式也以有氧运动或短期力量训练为主,对骨骼肌刺激更明显的长期抗阻力量训练或负重训练的研究较少,作用效果也不明确。国内外针对营养干预衰老的研究也较多,相关的营养补剂产品也层出不穷,但从整体、组织、基因不同层面入手,观察长期补充大豆天然提取物大豆多肽对骨骼肌衰老的影响并探讨其机制,国内外还没有见到相关文献的报道。
本研究就是运用衰老研究中常用的D-半乳糖皮下注射的方法,复制大鼠亚急性骨骼肌衰老模型,并在造模过程中和造模成功后都进行负重训练和补充大豆多肽的干预。通过观察一般指标、骨骼肌组织切片和相应的生化指标,判定两种干预方式对预防骨骼肌衰老过早出现和延缓骨骼肌衰老的作用效果,同时测量血清及骨骼肌超氧化物歧化酶(SOD)和丙二醛(MDA)、血清睾酮(T)、皮质醇(C)、生长激素(GH)和胰岛素样生长因子- I (IGF-I)、骨骼肌总蛋白和脂褐素、骨骼肌肌动蛋白(α-actin)、IGF-I和生长分化因子-8(GDF-8)mRNA等指标,初步探讨两种干预方式在预防和延缓骨骼肌衰老中的作用机制,为进一步进行人群干预试验积累一定的理论和实验基础,为提供更有针对性的运动方式和研制、开发合理有效的营养补剂,以对抗中老年人骨骼肌的衰老,开辟一条新思路和新途径。同时,也为指导中老年人科学的健身,合理进行慢性病的康复,提高健康水平和生活质量,提供一定的帮助和借鉴。
实验分为两部分:预防衰老实验和延缓衰老进程实验
一、预防衰老实验
3月龄SD雄性大鼠56只,随机分为7组:成年组(C)、D-半乳糖组(M)、D-半乳糖小负重组(S)、D-半乳糖大负重组(B)、D-半乳糖补肽组(P)、D-半乳糖补肽小负重组(PS)、D-半乳糖补肽大负重组(PB)。所有大鼠在6周D-半乳糖造模的过程中进行相应的负重训练和补充大豆多肽的干预。6周末处死,比较各组一般指标、骨骼肌组织切片、血清和骨骼肌组织生化以及分子生物学指标,结果如下:
1.一般指标:所有造模组大鼠均出现了衰老的外观特征,体重呈现自然增长趋势,双侧腓肠肌总重量、腓肠肌相对重量有下降的趋势,各干预组大鼠以上变化幅度趋缓;所有组大鼠每日摄食量都有下降的趋势,造模组趋势更为明显。提示:两种干预方式可以有效改善衰老的外部特征。
2.骨骼肌组织切片:光镜下观察C组大鼠为正常骨骼肌组织学特征,所有造模组大鼠均出现不同程度的肌细胞萎缩或退行性改变特征,以M组变化最为明显。提示:两种干预方式可以有效预防骨骼肌衰老过早的出现。
3.血清学指标:与C组相比,M组大鼠血清中SOD活力及SOD/MDA、T含量及T/C、GH含量显著下降,血清MDA含量、C含量显著上升,(P<0.01或P<0.05)血清IGF-I含量有下降的趋势,但无显著性差异;负重训练或补充大豆多肽干预可以有效的逆转以上趋势,均以小负重组表现更为明显,并且两种干预方式均具有显著的交互作用。提示:两种干预方式可以减轻D-半乳糖造成的机体脂质过氧化和激素水平的紊乱。
4.骨骼肌组织生化指标:与C组相比,M组大鼠骨骼肌SOD活力、MDA含量、脂褐素含量显著升高(P<0.01或P<0.05),SOD/MDA有降低的趋势,但无显著性差异;骨骼肌总蛋白含量显著下降(P<0.05);负重训练或补充大豆多肽干预除可以进一步提高骨骼肌SOD活力外,均可以逆转其他的趋势,多数以小负重组表现更为明显,并且以上情况两种干预方式均具有显著的交互作用。提示:两种干预方式可以减轻D-半乳糖造成的骨骼肌组织脂质过氧化和肌蛋白合成的减少。
5.骨骼肌组织分子生物学指标:与C组相比,M组大鼠骨骼肌组织中α-actin mRNA和IGF-I mRNA表达显著下降(P<0.01);GDF-8 mRNA表达显著升高(P<0.01);负重训练或补充大豆多肽干预可以有效的逆转以上的趋势,均以小负重组表现更为明显,并且两种干预方式均具有显著的交互作用。提示:两种干预方式可以升高D-半乳糖造成的骨骼肌组织α-actin mRNA和IGF-I mRNA的低表达,降低GDF-8 mRNA的高表达。
二、延缓衰老进程实验
3月龄SD雄性大鼠60只,随机分为8组:6周安静对照组(C6)、6周模型组(M6)、12周模型组(M12)、造模后大负重组(B12)、造模后小负重组(S12)、造模后补肽组(P12)、造模后补肽大负重组(PB12)、造模后补肽小负重组(PS12),14月龄SD雄性大鼠8只作为自然衰老组(OC)。除C6组、M6组、M12组和OC组,其余各组在6周D-半乳糖造模后进行相应的负重训练和补充大豆多肽的干预。分别于6周末和12周末处死相应组大鼠,测试相关指标,结果如下:
1. 6周组指标比较:与C6相比,M6组大鼠体重升高,腓肠肌总重量及相对重量均有降低的趋势,但均未达到统计学差异;血清SOD活力显著降低(P<0.05),血清MDA和骨骼肌脂褐素含量均显著升高(P<0.01);骨骼肌切片均出现不同程度的肌细胞萎缩或退行性改变特征。提示:造模成功。
2. 12周一般指标:所有造模组和OC组大鼠均出现了衰老的外观特征,各干预组大鼠衰老特征较轻;所有组大鼠体重呈现自然增长趋势,各干预组大鼠其幅度明显趋缓(P<0.05),两种干预方式具有显著的交互作用;两种干预方式使双侧腓肠肌总重量显著降低(P<0.05和P<0.01),有显著的交互作用,腓肠肌相对重量有降低的趋势,无显著的交互作用;各组大鼠每日摄食量呈现平稳增长的趋势,两种干预方式使增长幅度趋缓,无显著的交互作用。提示:造模成功后,再进行两种方式的干预,可以有效延缓衰老进程中的外部特征。
3. 12周骨骼肌组织切片:光镜下观察各组大鼠肌细胞形态有着不同程度的萎缩或退行性改变,以M12组和OC组变化最为明显,提示:造模成功后,再进行两种方式的干预,可以有效延缓骨骼肌衰老的进程。
4. 12周血清学指标:与OC组相比,M12组大鼠血清SOD活力、MDA含量以及SOD/MDA、血清T含量、C含量以及T/C、血清GH和IGF-I含量均无显著性差异。负重训练或补充大豆多肽可以显著提高血清SOD活力以及SOD/MDA、T含量以及T/C、GH和IGF-I含量,降低血清MDA含量和C含量,多数以小负重组表现更为明显,并且两种干预方式都具有显著的交互作用。(P<0.05或P<0.01)提示:造模成功后,再进行两种方式的干预,可以减轻机体脂质过氧化和激素水平的紊乱。
5. 12周骨骼肌组织生化指标:与OC组相比,M12组大鼠骨骼肌SOD活力、MDA含量及SOD/MDA、总蛋白含量和脂褐素含量均无显著性差异。负重训练或补充大豆多肽可以显著提高骨骼肌SOD活力及SOD/MDA、总蛋白含量,降低骨骼肌MDA含量和脂褐素含量,多数以小负重组表现更为明显,并且两种干预方式都具有显著的交互作用。(P<0.05或P<0.01)提示:造模成功后,再进行两种方式的干预,可以减轻骨骼肌组织脂质过氧化和肌蛋白合成的减少。
6. 12周骨骼肌组织分子生物学指标:与OC组相比,M12组大鼠骨骼肌α-actin mRNA、IGF-I mRNA和GDF-8 mRNA表达均无显著性差异。负重训练或补充大豆多肽干预可以提高骨骼肌α-actin mRNA和IGF-I mRNA的表达,降低GDF-8 mRNA的表达,均以小负重组表现更为明显,并且两种干预方式都具有显著的交互作用。(P<0.05或P<0.01)提示:造模成功后,再进行两种方式的干预,可以升高骨骼肌组织α-actin mRNA和IGF-I mRNA的低表达,降低GDF-8 mRNA的高表达。
结论
1. 6周D-半乳糖皮下注射,可以成功复制大鼠亚急性骨骼肌衰老模型。可能的作用机制为:①增多血液中自由基;②增强骨骼肌氧化应激以及脂质过氧化;③增加骨骼肌脂褐素的沉积;④促使激素及相关因子的代谢紊乱;⑤降低骨骼肌α-actin和IGF-I mRNA的表达,提高骨骼肌GDF-8 mRNA的表达。
2.负重训练或补充大豆多肽均可以有效的预防6周D-半乳糖造模过程中大鼠骨骼肌衰老过早的出现,以小负重训练效果最好,而且两种方式联合运用效果更为明显。
3. 6周负重训练或补充大豆多肽的干预均可以对6周D-半乳糖造模后大鼠骨骼肌衰老有积极的延缓作用,以小负重训练效果最好,而且两种方式联合运用效果更为明显。
4.负重训练和补充大豆多肽预防和延缓大鼠骨骼肌衰老的效果可能通过下列机制发挥作用:①减少血液中自由基;②减轻骨骼肌氧化应激以及脂质过氧化;③减少骨骼肌脂褐素的沉积;④纠正激素及相关因子的代谢紊乱;⑤提高骨骼肌α-actin和IGF-I mRNA的表达,降低骨骼肌GDF-8 mRNA的表达。
With the increasing of the world aging country and the proportion of old people, many countries face with the new and projecting problem of aging population. The governments and societies focus on how to improve people’s healthy life-span and life quality. The research in senescence and its correlated disease has been taking the worldwide medical subject invariably. At present, explore the essential of aging, search the effective antiaging agents and methods to prevent and postpone aging have become the hotspot study in the area of geriatric medicine. Recent years, the scientists pay more attention to the issue of decline of muscle function, because it can influence old people’s health. It is close correlative between the muscle function and senescence.
At present, most research about preventing and postponing aging focus on drugs. Although drugs have certain effect, their disadvantages of limitation and side effect are also obvious. Exercise is the basis of vital movement, and nutrition is the immediate guarantee of it. How to combine the exercise and nutrition together in an economic and safe way, make the organs and systems in a satisfactory condition, in order to confront the aging especially the muscle aging , it is worth to be studied thoroughly.
There are some correlative reports of exercise interference in aging. Although, most research are about the influence of whole function, the parameteres are limited and lack of the study in certain organ and tissue ,especially be short of the research in mechanism and comprehensive parameter of exercise interference in aging. Also, the exercise styles are in aerobic and short term strength training mostly, the patterns in long term strength and weight training which are more effective to the skeletal muscle are less, the affect are indefinite either. There are many studies of nutrition interference in aging in and out doors, the relative nutritional supplements are also to come out one after the other. Though, there is no correlated reports about the mechanism and effect of the long term soy polypeptide supplement in skeletal muscle aging from the aspects of whole body, tissue and genes.
The present research copys the rat subacute skeletal muscle aging model by the method of D-galactose hypodermic which is common in senescence study. And take the interference way in weight training and soy polypeptide supplement in and after the process of model making. The research aims to observe the general parameter, skeletal muscle tissue slice and biochemical parameter, in order to judge the prevention and postpone effect in skeletal muscle aging by the two interference ways. and to discuss the probable mechanisms by measuring serum & skeletal muscle superoxide dismutase (SOD) and malondealdehyde (MDA), serum testosterone(T), cortisol(C), growth hormone(GH) and insulin-like growth factor-1(IGF-I), skeletal muscle total protein level and lipofuscin, skeletal muscleα-actin,IGF-I and growth and differential factor-8(GDF-8) mRNA. With the purpose of accumulating the theory and experiment foundation in further human test, opening a new thinking and way to be against skeletal muscle aging in middle-old aged people by providing more direct exercise way and developing effective nutritional supplement. At the same time, it can provide some help of middle-old aged people in the direction of scientific body building, the reasonable recovery from chronic disease and the elevation of health level and quality of life.
The experiment is consisted of two parts, prevention aging part and delaying senility part.
Part I Prevention aging experiment
Fifty-six three month male Sprague-Dawley (SD) rats were randomly assigned into seven groups: adult group (C), D-galactose group (M), D-galactose small load exercise group(S), D-galactose big load exercise group (B), D-galactose peptide group (P), D-galactose peptide and small load exercise group(PS), D-galactose peptide and big load exercise group (PB). All the rats were taken the interference way in weight training and soy polypeptide supplement in the process of 6w D-galactose hypodermic. By the end of 6th week, all rats were killed and serum and skeletal muscle parameters were evaluated.
1. General parameter: All the model rats showed up the aging appearances, the body weight were in normal increase trend, di-gastrocnemius &relative weight were in the decrease trend ,and all the rats in interference group could slow down the above trend; All the rats quotidie ingestion were in the decrease trend, the model groups were in obvious way. Results indicate that two interference way can improve the aging appearances effectively.
2. Skeletal muscle tissue slice: Under light microscope, the rats in group C were in normal skeletal muscle histologic characteristics, All the model rats showeg up muscle cell atrophy or regressive changes in a different level, especially the rats in group M. Results indicate that two interference way can prevent the premature appearance in skeletal muscle aging.
3. Serum parameter: Compare with group C, the serum SOD, SOD/MDA, T, T/C and GH in group M were lower, MDA and C were higher.(significant or very significant difference, P<0.05 or P<0.01), but serum IGF-I was in decrease trend and had no statistic difference; Weight training or soy polypeptide supplement could reverse the trend, the groups of small load all had more obvious appearance, and they had notable interaction. Results indicate that two interference way can alleviate organism lipid peroxidation and hormone abnormality due to D-galactose.
4. Skeletal muscle biochemical parameter: Compare with group C, the skeletal muscle SOD, MDA and Lipofuscin in group M were higher (significant or very significant difference, P<0.05 or P<0.01), but SOD/MDA was in decrease trend and had no statistic difference (P>0.05), skeletal muscle total protein level was lower(significant difference, P<0.05); Weight training or soy polypeptide supplement could make skeletal muscle SOD in a further increase and reverse the rest trend, the groups of small load had more obvious appearance in majority, also they had notable interaction. Results indicate that two interference way can alleviate skeletal muscle lipid peroxidation and low myoprotein synthesis due to D-galactose.
5. Skeletal muscle molecular biological parameter:Compare with group C, the skeletal muscleα-actin mRNA and IGF-I mRNA in group M were lower,but GDF-8 mRNA was higher(very significant difference, P< 0.01); Weight training or soy polypeptide supplement could reverse the trend, the groups of small load all had more obvious appearance, and they had notable interaction. Results indicate that two interference way can increase the low expression ofα-actin mRNA and IGF-I mRNA and decrease the high of GDF-8 mRNA due to D-galactose.
Part II Delaying senility experiment
Sixty three month male SD rats were randomly assigned into eight groups: 6w control group (C6), 6w model group (M6), 12w model group (M12), small load exercise group(S12), big load exercise group (B12), peptide group (P12), peptide and big load exercise group (PB12),peptide and small load exercise group(PS12)), eight fourteen month male SD rats were taken the natural aging group(OC). Besides the group C6, M6, M12 and OC, all the other rats were taken the interference way in weight training and soy polypeptide supplement after 6w D-galactose hypodermic. By the end of 6th week and 12th week, the corresponding rats were killed and serum and skeletal muscle parameters are evaluated.
1.Comparison between group C6 and M6: Compare with group C6, the di-gastrocnemius &relative weight in group M6 were in the decrease trend, though they had no statistic difference; the serum SOD in group M6 was lower (significant difference, P<0.05), serum MDA and skeletal muscle lipofuscin were higher (very significant difference P<0.01), All the skeletal muscle tissue slices showed up muscle cell atrophy or regressive changes in a different level. These results indicate that the skeletal muscle aging model is successful.
2. General parameter of 12 week: All the model rats and group OC showed up the aging appearances, the rats in interference group could slow down the above trend; The body weight in all groups were in normal increase trend, the rats in interference group could slow down it obviously(significant difference, P<0.05),and two interference way had notable interaction; two interference way could make di-gastrocnemius &relative weight in the decrease trend(significant or very significant difference, P<0.05 or P<0.01), and maked it relative weight in a decrease trend; All the rats quotidie ingestion were in the increase trend, two interference way could make it in a reverse way, but had no notable interaction .Results indicate that two interference way can improve the aging appearances effectively after the process of model.
3. Skeletal muscle tissue slice of 12 week: Under light microscope, All the model rats showed up muscle cell atrophy or regressive changes in a different level, especially the rats in group M12 and OC. Results indicate that two interference way can postpone the course in skeletal muscle aging after the process of model.
4.Serum parameter of 12 week: Compare with group OC, the serum SOD, MDA, SOD/MDA, T, C, T/C, GH and IGF-I in group M12 had no statistic difference. Weight training or soy polypeptide supplement could increase the content of serum SOD, SOD/MDA, T, T/C, GH and IGF-I, decreased the content of serum MDA and C, the groups of small load had more obvious appearance in majority, and they had notable interaction. (significant or very significant difference, P<0.05 or P<0.01).Results indicate that two interference way can alleviate organism lipid peroxidation and hormone abnormality after the process of model.
5. Skeletal muscle biochemical parameter of 12 week: Compare with group OC, the skeletal muscle SOD, MDA, SOD/MDA, total protein level and lipofuscin in group M12 had no statistic difference. Weight training or soy polypeptide supplement could increase the content of skeletal muscle SOD, SOD/MDA and total protein level, decreased the content of skeletal muscle MDA and lipofuscin, the groups of small load had more obvious appearance in majority, and they had notable interaction. (significant or very significant difference, P<0.05 or P<0.01). Results indicate that two interference way can alleviate skeletal muscle lipid peroxidation and low myoprotein synthesis after the process of model.
6. Skeletal muscle molecular biological parameter of 12 week:Compare with group OC, the skeletal muscleα-actin mRNA and IGF-I mRNA in group M12 had no statistic difference. Weight training or soy polypeptide supplement could increase the expression ofα-actin mRNA and IGF-I mRNA, decreased the expression of GDF-8 mRNA, the groups of small load all had more obvious appearance, and they had notable interaction. Results indicate that two interference way can increase the low expression ofα-actin mRNA and IGF-I mRNA , decrease the high of GDF-8 mRNA after the process of model.
Conclusions
1. Rat skeletal muscle aging model can be copied successfully by 6 week D-galactose hypodermic and the probable pathogenesy are as follows:①increase the blood free radical;②increase skeletal muscle oxidative stress and lipid peroxidation;③increase the deposition of lipofuscin in skeletal muscle;④promote the metabolic disorder of hormone and correlation factors;⑤decrease the expression of skeletal muscleα-actin mRNA and IGF-I mRNA, increase the expression of skeletal muscle GDF-8 mRNA.
2. Weight training or soy polypeptide supplement can prevent the premature appearance in skeletal muscle aging resulted from 6 week D-galactose model effectively, the exercise of small load has the best result, and the two interference way united can have more obvious effect.
3. 6 week weight training or soy polypeptide supplement can have an active postpone effect of skeletal muscle aging after the 6 week D-galactose model, the exercise of small load has the best result, and the two interference way united can have more obvious effect.
4. The mechanisms of preventive and postponed effect of weight training and soy polypeptide supplement in skeletal muscle aging are probably as follows:①decrease the blood free radical;②decrease skeletal muscle oxidative stress and lipid peroxidation;③decrease the deposition of lipofuscin in skeletal muscle;④correct the metabolic disorder of hormone and correlation factors;⑤i ncrease the expression of skeletal muscleα-actin mRNA and IGF-I mRNA, decrease the expression of skeletal muscle GDF-8 mRNA.
引文
[1]窦玉沛.应对人口老龄化的挑战加快老年社会福利事业的发展[J].理论前沿,2000,24:18-20.
[2]安红梅,胡兵.肾虚衰老理论研究的新思路[J].中国中医基础医学杂志,2004,10(2): 42-44.
[3]许豪文.运动和衰老(上)[J].体育科研,1998,19(2):1-2.
[4]印大中.衰老研究的新纪元[J].生命科学研究,2000, 4(2): 95-101.
[5]刘汴生.衰老的动态变化与抗衰老对策[J].实用老年医学,1998,12(2):73-74.
[6]许豪文.运动生物化学[M].北京:高等教育出版社,2001:346-347.
[7]Vihra BP, Sharma SP, Kansal VK. Age-dependent variations in mitochondrial and cytosolic antioxidant enzymes and lipid peroxidation in different regions of central nervous system of guinea pigs[J]. Indian J Biochem Biophys, 2001,38(5):321-326.
[8]Jang I, JungK, Cho J. Age-related changes in antioxidant enzyme activities in the small intestine and liver from Wistar rats[J]. Exp Anim, 1998,47(4):247-252.
[9]Inal M E,Kanbsk G,Sunal E. Antioxidant enzyme activities and malondialdehyde levels related to aging[J]. Clip Chin Acta , 2001,305(1):75-80.
[10]Wei YH, Lu C Y, Wei C Y, et al. Oxidative stress in human aging and mitochondrial disease-consequences of defective mitochondrial respiration and impaired antioxidant enzyme system[J]. Chin J Physiol, 2001,44(1):1-11.
[11]Kim H C, Bing G Y, Jhoo W K, et al. Oxidative damage causes formation of lipofuscin- like substances in the hippo campus of the senescence-accelerated mouse after kainate treatment[J]. Behav Brain Res, 2002, 131(1-2):211-220.
[12]Gil P, Farinas F, Casado A, et al. Malondialdehyde:a possible marker of ageing[J]. Gerontology, 2002,48(4):209-214.
[13] Stadtman ER. Protein oxidation and aging[J]. Science,1992,257:1220.
[14]龚国清,徐散本.小鼠衰老模型研究[J].中国药科大学学报,1991,22(2):101-103.
[15]马鹤雯,张玉静,阮承迈等.端粒(酶)同癌症与衰老关系的研究进展[J].国外医学·遗传学分册,2000, 23(3): 163-I65.
[16]Martens JW, Sieuwerts AM, Vries JB, et al. Aging of stromal-derived human breast fibroblasts might contribute to breast cancer progression[J]. Thromb Haemost, 2003, 89(2):393-404.
[17]张开红.端粒与端粒酶[J].医学综述,2000, 6(5): 196-199.
[18]Tzukerman M,Selig S,Skorecki K. Telomeres and teloemerase in human health and disease[J]. J Pediatr Endocrinol Metab,2002,15(3):229-240.
[19]杨宇,李发元,胡信群等.衰老小鼠端粒酶活性的测定及意义[J].中国老年学杂志,2002,22(4):266.
[20]Johansson A, Koskiniemi S, Gottfridsson P, et al. Multiple-locus variable-number tandem repeat analysis for typing of Staphylococcus epidermidis[J]. J Clin Microbiol,2006, 44(1):260-265.
[21]Schjeide BM, Hooli B, Parkinson M. GAB2 as an Alzheimer Disease Susceptibility Gene: Follow-up of Genomewide Association Results[J]. Arch Neurol,2009,66(2):250-254.
[22]Stevens JB, Shephered JM, Vories PA,et al. A mixture of mivacurium and rocuronium is comparable in clinical onset to succinylcholine[J]. J Clin Anesth, 1996,8(6):486-90.
[23]马宏,张宗玉,童坦君等.衰老的生物学标志[J].生理科学进展,2002,33(1):65-68.
[24]WangY,MichikawaY,MallidisC,et al. Mussel-specific mutations accumulate with aging in critical human mtDNA control sites for replication[J]. Pros Natl Acad Sci USA,2001,98 (7): 4022-4027.
[25]Harihara S,Nakamura K,Takubo K,et al. Comparison of the level of mitochondrial DAN A3243G mutation in esophageal epithelium and myocardium from individuals of very advanced age[J]. Exp Gerontol,2002,37(7):917-923.
[26]Barazzoni R, Short KR, Nair KS. Effects of aging on mitochondrial DNA copy number and cytochrome c oxidese gene expression in rat skeletal muscle,liver and heart[J]. J Biol Chem,2000,275 (5):3343-7.
[27]Khaidakov M,Heflich RH,Manjanatha MG, et al. Accumulationof point mutations in mitochondrial DNA of aging mace[J]. Muta t Res, 2003,52b(1-2): 1-7.
[28]钱杰,张丽容.衰老小鼠线粒体DNA缺失的研究[J].中国老年学杂志,2003,23(1):43-44.
[29]夏寿萱.放射生物学[M].北京:军事医学出版社,1998.22-44.
[30]崔英俊,李庆章.滑菇多糖对衰老模型鼠不同时期免疫功能的影响[J].东北农业大学学报,2004,35(2):129-134.
[31]陈友琴,胡新珉,刘鸿莲等. YN-PTOL对03衰老模型自由基损伤的保护作用[J].中国医学物理学杂志,2000,17(l):57-58.
[32]董晓华,张丹参,武海霞.衰老动物模型的研究进展及评价[J].河北北方学院学报2004,21(6):41-43.
[33]卫生部.《保健食品功能学检测程序与方法》[S].1996.
[34]赵鹏,杨玉英.半乳糖制备亚急性衰老动物模型的可行性(综述)[J].中国食品卫生杂志,1999,11(1):52-53.
[35]陈勤.抗衰老研究实验方法[M].北京:中国医药科技出版社,1996:46-47.
[36]Ho SC, Liu JH, Wu RY. Establishment of the mimetic aging effect in mice caused by D-galactose[J]. Biogerontology, 2003;4(1):15-8.
[37]徐智,吴国明,钱桂生等.大鼠衰老模型的初步建立[J].第三军医大学学报,2003;25(4): 312-315.
[38]刘晓秋,李卫东,唐惠琼等. D-半乳糖衰老大鼠自由基代谢状况分析[J].中国老年学杂志,2001, 21 (6 ): 456-458.
[39]徐叔云.药理实验方法学[M].北京:人民卫生出版社,2001:1464-1466.
[40]Edstrom E, Altun M, Hagglund M, et al. Atrogin-1/MAFbx and MuRF1 Are Downregulated in Aging-Related Loss of Skeletal Muscle[J]. J Gerontol A Biol Sci Med Sci. 2006,61(7):663-674.
[41]沙继斌.骨骼肌衰老的研究进展[J].山东体育学院学报,2002,18(2):43-46.
[42]邓树勋.运动生理学[M].北京:高等教育出版社,1999:473.
[43]Johnston AP, De Lisio M, Parise G. Resistance training, sarcopenia and the mitochondrial theory of aging[J]. Appl Physiol Nutr Metab,2008 ,33(1):191-199.
[44]ZackerRJ. Health-related implications and management of sarcopenia[J]. JAAPA,2006, 19(10):24-29.
[45]R?ckl KS, Hirshman MF, Brandauer J, et al. Skeletal muscle adaptation to exercisetraining: AMP-activated protein kinase mediates muscle fiber type shift[J]. Diabetes, 2007 ,56(8):2062-2069.
[46]Lytras A, Tolis G. Assessment of endocrine and nutritional status in age-related catabolic states of muscle and bone[J]. Curr Opin Clin Nutr Metab Care,2007,10(5):604-610.
[47]Young A, et al. Size and strength of the quadriceps muscle of old and young women[J]. Eur J Clin Invest, 1984(14): 282-287.
[48]Young A,et al. Ihe size and strength of the quadriceps muscle of old and young men[J]. Clin. Physiol, 1985(5): 145-154.
[49]王润平,任涵.老年体育研究进展[J].西北师范大学学报:自然科学版, 2002,38(1):112-116.
[50]Mcmurdo M and L.Rennier. Improvements in quadriceps strength with regular seated exercise in the institutionalized elderly[J]. Arch. Phys. Med. Rehabil,1994,75:600-603.
[51] Wikipedia网站[OL].http://www.the free encyclopedia.com.
[52]Haus JM, Carrithers JA, Trappe SW,et al. Collagen, cross-linking, and advanced glycation end products in aging human skeletal muscle[J]. J Appl Physiol,2007, 103(6):2068-2076.
[53]Takahashi K, Takahashi HE, Nakadaira H, et al. Different changes of quantity due to aging in the psoas major and quadriceps femoris muscles in women[J]. J Musculoskelet Neuronal Interact,2006,6(2):201-205.
[54]满君.增龄骨骼肌的机能特征及运动对其影响(综述)[J].北京体育大学学报,2001,24(2):200-202.
[55]Synder R J. Effect of testosterone treatment on bodycomposition and muscle strength in men over 65 old years[J]. J. Clin. Endocrinol. Metab,1999,84:2647-2653.
[56]Morles A. J. Effect of replacement dose of dehydroepiandrosterone in men an women of advancing age[J]. J. Clin. Endocrinol. Metab,1994,78:1360-1367.
[57]ButterfieldG.E. Effect of rhGH and rhIGF-I treatmenton protein utilization in elderly women[J]. Am. J. Physiol,1997,272:94-99.
[58]徐秀英,李骁君,王广峰. 6周递增负荷训练对大鼠骨骼肌IGF-I及血清GH—IGF-I水平影响的研究[J].山东体育学院学报,2001,17(4):34-35.
[59]Lunenfeld B, Nieschlag E. Testosterone therapy in the aging male[J]. Aging Male,2007,10(3):139-153.
[60]Machida S, Narusawa M. The roles of satellite cells and hematopoietic stem cells in impaired regeneration of skeletal muscle in old rats[J]. Ann N Y Acad Sci,2006 ,1067:349-353.
[61]Barton-Davis E R. Viral mediated expression of insulin-like growth factorⅠblocks the ageing-related loss of skeletal muscle function[J]. Proc. Natl. Acad. Sci.,1998,95:5603-5607.
[62]Welle S. Growth hormones increases muscle mass and strength but does not rejuvenate myofibrillar protein synthesis in healthy subjects over 60 years old[J]. J. Clin.Endocinol. Metab,1996,81:3239-3243.
[63]Stitt TN, Drujan D, Clarke BA, et al. The IGF-I/PI3K/Akt pathway prevents expression of muscle atrophy-induced ubiquitin ligases by inhibiting FOXO transcription factors [J]. Mol Cell, 2004,14(3):395-403.
[64]Roubenoff R. Origins and Clinical Relevance of Sarcopenia[J]. Canadian Journal of Applied Physiology, 2001.26(1):78-89.
[65]Morley JE, Baumgartner RN, Roubenoff R,et al. Sarcopenia[J]. J Lab Clin Med. 2001,137(4):231-243.
[66]Dupont-Versteegden E E. Apoptosis in muscle at rophy : Relevance to Sarcopenia [J] . Exp Gerontol ,2005 (40) :473-481.
[67]Murlasits Z, Cutlip R G, Geronilla K B, et al. Resistance training increase heat shock protein levels in skeletal muscle of young and old rats[J]. ExpGerontol,2006,41:398-406.
[68]Deschenes MR. Effects of aging on muscle fibre type and size[J]. Sports Med. 2004,34(12):809-824.
[69]牛嗣云.松花粉抗下丘脑-垂体-睾丸衰老机理的实验研究[D].石家庄:河北医科大学,2006.
[70]Paddon-Jones D. Interplay of stress and physical inactivity on muscle loss: nutritional countermeasures[J]. J Nut, 2006 Aug;136(8):2123-2126.
[71]Karakelides H, Nair KS. Sarcopenia of aging and its metabolic impact[J]. Curr Top Dev Biol. 2005(68):123-148.
[72]Geoffrey G,Stephen D R Harridge. Growth factors and muscle aging [J]. Exp Gerontol, 2004(39) :1433-1438.
[73]Goldspin K G. Impairment of IGF-I gene splicing and MGF expression associated with muscle wasting [J]. Int J Biochem Cell Bio ,2006, (38) :481-489.
[74]Sanoudou D, Corbett MA, Han M, et al. Skeletal muscle repair in a mouse model of nemaline myopathy[J]. Hum Mol Genet. 2006,15(17):2603-12.
[75]McNeil CJ, Doherty TJ, Stashuk DW, et al. Motor unit number estimates in the tibialis anterior muscle of young, old, and very old men[J]. MuscleNerve,2005,31(4):461-467.
[76]Susan V. Skeletal muscle weakness in old age:underlying mechanisms[J]. Med. Sci. Sports Exerc,1994,26(4):432-439.
[77]Carlson BM. Muscle transplantation between young and old rats: age of host determines recovery [J]. Am. J.Physiol,1998,256:1262-1266.
[78]Thomas DR. Loss of skeletal muscle mass in aging: examining the relationship of starvation, sarcopenia and cachexia[J]. Clin Nutr. 2007,26(4):389-399.
[79]SharmanMJ,Newton RU,Triplett-McBride T, et al. Changes inmyosin heavy chain composition with heavy resistance training in 60 to 75-year-old men and women[J]. J Appl Physiol,2001,84(1-2):127-132
[80]逄金柱,王瑞元. 2周耐力训练对大鼠骨骼肌肌动蛋白和肌球蛋白重链基因表达的影响[J].中国运动医学杂志,2005 24(4):415-418.
[81]Tajsharghi H, Sunnerhagen KS, Darin N, et al. Induced shift in myosin heavy chain expression in myosin myopathy by endurance training[J]. JNeurol.2004 ,251(2):179-83.
[82]Short KR, Vittone JL, Bigelow ML,et al. human skeletal muscle with age and endurance exercise training[J]. J Appl Physiol,2005,99(1):95-102.
[83]Marx JO, KraemerWJ, Nindl BC,et al. Effects of ging on human skeletal muscle myosin heavy-chain mRNA content and protein isoform expression[J]. J Gerontol A Biol Sci Med Sci,2002,57(6):B232-238.
[84]Vittorio S.Muscle-specific gene expression: a comparison of cardisc and skeletal muscle transcription strategies[J]. Circulation Research, 1993,72(5):925-931.
[85]Joanna Szczepanowska. Effects of denervation and muscle inactivity on organization ofF-actin[J]. Muscle Nerve,1998(21):309-317.
[86]Riley D A.Disproportionate loss of filaments in humansoleus muscle after 17-day bed rest[J].Muscle Nerve,1998,21:1280-1289.
[87] Thomason D B.Altered actin and myosin expression inmuscle during exposure to microgravity[J].J Appl Physiol,1992,73(2):90-93.
[88]McPherron AC, Lawler AM, Lee SJ. Regulation of skeletal muscle mass in mice by a new TGF-βsuperfamily member[J].Nature,1997,387(6628):83-90.
[89]Lee SJ, McPherron AC. Regulation of myostatin activity and muscle growth[J]. Proc Natl Acad Sci USA, 2001,98:9306-9311.
[90]Szabo G, Dallmann G, Muller G, et al. A deletion in the myostatin gene causes the compact (Cmpt) hypermuscular mutation in mice[J]. Mamm Genome, 1998,9:671-672.
[91]Sakuma K, Watanabe K, Sano M, et al. Differential adaptation of growth and differentiation factor 8/myostatin, fibroblast growth factor 6 and leukemia inhibitory factor in overloaded regenerating and denervated rat muscles[J]. Biochim Biophys Acta, 2000(1497):77-88.
[92]高丽,隋波,亓新学等.不同运动方式对后肢固定大鼠腓肠肌肌肉生长抑制素mRNA表达的影响[J].中国运动医学杂志,2008,7;27(4):492-494.
[93]Lalani R, Bhasin S, Byhower F, et al. Myostatin and insulin-like growthfactor-Ⅰand-Ⅱexpression in the muscleof rats exposed to the microgravity environment of the NeuroLab space shuttle flight[J]. J Endocrinol, 2000, 167(3):417-428.
[94]Reardon K A, Davis J, Kapsa R M I et al. Myostatin,insulin-like growth factor-1,and leukemia inhibitory factor mRNAs ere upregulated in chronic human disuse muscle atmphy[J]. Muscle Nerve, 2001, 24, 893-899.
[95]Marcell T J, Harman S M, Urban R J, et al. Comparison of GH, IGF-I, and testosterone with mRNA of receptors and myostatin in skeletal muscle in older men [J]. Am J Physiol Endocrinol Metab, 2001, 281(6):E1159-1164.
[96]Gonzalez-Cadavid NF, Taylor WE, Yarasheski K, et al. Organization of the human myostatin gene and expression in healthy men and HIV-infected men with muscle wasting[J]. Proc Natl Acad Sci U S A,1998 ,95(25):14938-14943.
[97]Yamanouchi K, Soeta C, Naito K, et al. Expression of myostatin gene in regenerating skeletal muscle of the rat and its localization[J]. Biochem Biophys Res Commun, 2000(270):510-516.
[98]Conlon I, Raff M. Size control in animal development[J]. Cell,1999(96):235-244.
[99]Sandri M, Sandri C, Gilbert A, et al. Foxo transcription factors induce the atrophy-related ubiquitin ligase atrogin-1 and cause skeletal muscle atrophy[J]. Cell,2004, 117(3):399-412.
[100]Goldspink G. Loss of muscle strength during aging studied at the gene level[J]. Rejuvenation Res,2007,10(3):397-405.
[101]药立波.医学分子生物学[M].北京:人民卫生出版社,2004:257-262.
[102]陈吉棣.有氧运动、基因表达和慢性病[J ].中国运动医学杂志,2002, 21 (1) : 61-65.
[103]Martin AD, Spenst LF, Drinkwater DT, et al. Anthropometric estimation of muscle mass in men[J]. Med Sci Sports Exerc,1990 ,22(5):729-733.
[104]Fahim MA. Morphological correlates of physiological responses in partially denervated mouse muscle during aging[J]. Int J Dev Neurosci, 1993,11(3):303-310.
[105]Latham N K, Anderson C S, Lee A, et al. A randomized, controlled trial of quadriceps resistance exercise and vitamin D in frail older people : the Frailty Interventions Trial in Elderly Subjects (FITNESS)[J]. Am Geriatr Soc, 2003, 51(4): 291-299.
[106]朱志祥.运动和衰老[J].体育科学,2004,24(7): 37-43.
[107]Visser M, Goodpaster BH, Kritchevsky SB, et al. Muscle mass, muscle strength, and muscle fat infiltration as predictors of incident mobility limitations in well-functioning older persons[J]. J Gerontol A Biol Sci Med Sci,2005,60(3):324-333.
[108]Neil McCartney,et al. A longitud;nal trial of weight training the elderly continued improvements in two years[J]. Journal of Gerontology,1995, 51A(5):425-438.
[109]Sallinen J, Pakarinen A, Fogelholm M, et al. Dietary intake, serum hormones, muscle mass and strength during strength training in 49-73-year-old men[J]. Int J Sports Med,2007,28(12):1070-1076.
[110]Anton MM, Cortez-Cooper M, Devan AE,et al. Resistance Training Increases Basal Limb Blood Flow and Vascular Conductance in Aging Humans[J]. J Appl Physiol,2006101(5):1351-5.
[111]Santtila M, Keijo H, Laura K,et al. Changes in cardiovascular performance during an 8-week military basic training period combined with added endurance or strength training[J]. Mil Med, 2008,173(12):1173-1179.
[112]刘宇,彭千华,田石榴.老年人肌力流失与肌肉疲劳的肌动图研究[J].体育科学,2007,27(5) :57-64.
[113]Salminen A , Vihko V. Effects of age and prolonged running on proteolytic capacity in mouse cardiac and skeletal muscles[J]. Acta Physiol Scared, 1981(112):89- 95.
[114]Proctor D N, Balagopal P, Nair KS. Age-related with re-duced sarcopenia in humans is associated synthetic rated of specific muscle proteins[J]. J Nutr, 1998,(128):5351-5335.
[115]Hayes A, Cribb PJ. Effect of whey protein isolate on strength, body composition and muscle hypertrophy during resistance training[J]. Curr Opin Clin Nutr Metab Care,2008 ,11(1):40-4.
[116]许豪文.运动和衰老(下)[J].体育科研,1998,19(3): 16-21.
[117]李世成.补充大豆肽对一次离心运动后骨骼肌微结构损伤的作用及其机制研究[D].北京:北京体育大学,2004.
[118]赵芳芳.大豆肽的生物学功能研究[D].北京:中国农业大学,2004.
[119]高春霞.大豆多肽生理活性、应用与前景分析[J].大豆通报,2006,(4):18-22.
[120]张美莉主编.食品功能成分的制备及其应用[M].北京:中国轻工业出版社, 2007:117-119.
[121]杨金兰.大豆功能因子的功能作用[J].大豆通报,2005,3:28-29.
[122]陈历俊.大豆活性肽的研制与应用——大豆深加工研究系列之一[D].长春:东北农业大学,1998.
[123]陈晓光,金红梅,胡薇.大豆肽的生理功能及应用前景[J].中国食物与营养,2000(4):39-41.
[124]青山敏明. Recent Advances in the nutritional physiology of soy protein and its peptide[J].食品与开发,1998,7:15-16.
[125]赵秀娟,王小雪等.大豆活性肽粉对饲喂高脂饲料大鼠血脂的影响[J].中国卫生检验杂志,2002,12(4):421-422.
[126]江河源,吕飞杰,邰建祥.大豆种生物活性成分及其功能[J].大豆科学,2000,(19)2:160-161.
[127]崔洪斌.大豆生物活性物质的开发与应用[M ].北京:中国轻工业出版社,2001:257.
[128]高长城,胡锐,李煌馨.大豆肽对增强体能的作用[J].大豆通报,2001(2):24.
[129]Chen H M, Muramoto K, Yamauchi F. Structural analysis of antioxidative peptides form soybean beta-conglycinin[J]. USA: Journal of agricultural and food chemistry,1998. 43(3): 574-578.
[130]张莉莉,王恬.大豆源生物活性肽的研究进展[J].中国油脂,2005,30(4):33-36.
[131]石岗.生物活性肽在动物生产中的应用[J].畜牧与兽医,2002,34(7):38.
[132]Takahiro Tsuruki, Katsuki Kishi, Masakazu Takahashi,et al. Soymetide, an immunostimulating peptide derived from soybean L-conglycinin, is an fMLP agonist[J]. FEBS Letters, 2003(540):206-210.
[133]赵秀娟,吴坤,崔洪斌.大豆活性肽粉的免疫调节作用的试验研究[J].大豆活性物质的研究,2002.
[134]Park MH, Song EY, Ahn C, et al. Two subtypes of hepatitis B virus-associated glomerulonephritis are associated with different HLA-DR2 alleles in Koreans[J]. Tissue Antigens, 2003,62(6):505-511.
[135]Stroescu V, Dragan J, Simionescu L, et al. Hormonal and metabolic response in elite female gymnasts under going strenuous training and supplementation with SUPRO Brand Isolated Soy Protein[J]. J Sports Med Phys Fitness, 2001, 41(1):89-94.
[136]Dr?gan I, Stroescu V, Stoian I,et al. Studies regarding the efficiency of Supro isolated soy protein in Olympic athletes[J]. Rev Roum Physiol,1992,29(3-4):63-70.
[137]中华人民共和国卫生部新闻中心. [OL].http://www.moh.gov.cn/newshtml/20978.htm
[138]荣建华.大豆多肽及其生物活性的研究[D].武汉:华中农业大学,2001.
[139]袁书林,陈海燕,王宵燕等.小肽营养研究进展[J].粮食与饲料工业, 2002(8): 37-39.
[140]孔庆学,甄润英,李玲.大豆蛋白水解物—功能性低聚肽物质的开发研究[J].天津农学院学报, 2002, 9(3): 3-4.
[141]Tohru Fushiki. Effects of the soybean protein on an increase in muscle mass during training in mice[J]. Rep soybean protein Res Com,1994(15):51-56.
[142]魏源.补充活性肽和人参对离心运动后骨骼肌微损伤及其修复效果的观察研究[D].北京:北京体育大学,2005.
[143]王启荣,李肃反,扬则宜,等.补充大豆多肽对中长运动员训练期生化指标的影响[J] .中国运动医学杂志,2004 ,23(1) :33 - 37.
[144]李世成,杨则宜.活性肽及其在运动中的应用[J].中国运动医学杂志, 2003,22(2): 174-176.
[145]林华,于文谦.人体衰老机理及有氧运动对延缓衰老的作用[J].体育学刊, 2000(2);28-30.
[146]贤均.抗衰老研究729篇文献计量分析[J].中国科技期刊研究,1999(1):85.
[147]Morley JE.Weight loss in older persons: new therapeutic approaches[J]. Curr Pharm Des, 2007,13(35):3637-3647.
[148]P?ll?nen E, Ronkainen PH, Suominen H,et al. Muscular transcriptome in postmenopausal women with or without hormone replacement[J]. Rejuvenation Res,2007,10(4):485-500.
[149]Ottenbacher KJ, Ottenbacher ME, Ottenbacher AJ,et al. Androgen treatment and muscle strength in elderly men: A meta-analysis[J]. J Am Geriatr Soc, 2006,54(11):1666-73.
[150]Lee CE, McArdle A, Griffiths RD. The role of hormones, cytokines and heat shock proteins during age-related muscle loss[J]. Clin Nutr, 2007,26(5):524-534.
[151]Brand TC, Canby-Hagino E, Thompson IM. Testosterone replacement therapy and prostate cancer: a word of caution[J]. Curr Urol Rep, 2007,8(3):185-189.
[152]Solomon AM, Bouloux PM.Modifying muscle mass-the endocrine perspective[J]. J Endocrinol, 2006,191(2):349-360.
[153]Wilkinson SB, Phillips SM, Atherton PJ,et al. Differential effects of resistance and endurance exercise in the fed state on signalling molecule phosphorylation and protein synthesis in human muscle[J]. J Physiol, 2008 ,586(15):3701-3717.
[154]Lebrun CE, Schouw YT, de Jong FH,et al. Fat mass rather than muscle strength is the major determinant of physical function and disability in postmenopausal women younger than 75 years of age[J]. Menopause,2006,13(3):474-481.
[155]Nair-Shalliker V, Kee AJ, Joya JE, et al. Myofiber adaptational response to exercise in amouse model of nemaline myopathy[J]. Muscle Nerve,2004 ,30(4):470-480.
[156]Suetta C, Magnusson SP, Beyer N,et al. Effect of strength training on muscle function in elderly hospitalized patients[J]. Scand J Med Sci Sports, 2007 ,17(5):464-472.
[157]Di Iorio A, Abate M, Di Renzo D, et al. Sarcopenia: age-related skeletal muscle changes from determinants to physical disability[J]. Int J ImmunopatholPharmacol,2006,19(4): 703-719.
[158]Bedford TG, Tipion CM, Nilson NC, et al. Maximum oxygen consumption of rats and its changes with various experimental procedure[J]. J Appl Physiol, 1979, 47(6):1278- 1283.
[159]闫万军.负重跑训练改善老龄大鼠肌肉丢失的效果与机理[D].石家庄:河北师范大学,2008.
[160]壄中征哉著.临床肌肉病理学[M].吴士文,马维娅译.北京:人民军医出社,2007:10.
[161]薛红丽,赵佩霞.衰老小鼠皮层NO、MDA、SOD水平变化及其相互关系的研究[J].中国老年学杂志,2000,20(2):89-90.
[162]梁艳菊.四君子汤对D-半乳糖致衰老模型大鼠抗衰老作用的实验研究[D].广州:暨南大学,2005.
[163]沈志祥.运动与衰老[J].体育科学,2004,24(7):37-43.
[164]卫小梅,郭铁成.悬吊运动疗法—一种主动训练及治疗肌肉骨骼疾患的方法[J].中华物理医学与康复杂志,2006,28(4):281-283.
[165]Bradl I, Morl F, Scholle HC, et al. Back muscle activation pattern and spectrum in defined load situations[J]. Pathophysiology, 2005, 12: 275-280.
[166]张保国,王小迪,王安利.本体感觉神经肌肉促进技术治疗大学生一次离心运动后小腿三头肌延迟性肌肉酸痛的效果[J].中国运动医学杂志,2007, 26(6):740-742.
[167]王静.抗阻练习对衰老大鼠骨骼肌中IGF-I, MGF及肌肉生长抑制素的影响[D].上海:华东师范大学,2008.
[168]卢健,陈彩珍,许永刚等.小鼠运动方式——转笼的制作与应用[J].广州体育学院学报,2002,22(5):26-28.
[169]史仍飞,卞玉华,危小焰.振动训练对大鼠骨骼肌质量和肌细胞机械生长因子mRNA表达的影响[J].中国运动医学杂志,2008,27(4):508-510.
[170]Levenhagen D K, Carr C, Carlson MG, et al. Postexercise protein intake enhances whole-body and leg protein accretion in humans[J]. Med Sci Sports Exerc,2002,34(5): 828-837.
[171]Luc J C and Van loon. Ingestion of Protein Hydrolysate and Amino Acid-carbohydrate Mixtures Increases Postexercise Plasma Insulin Responses in Men[J]. J Nutr,2000(130):2508-2513.
[172]陈成.大豆蛋白活性肽保健功能性的研究[J].大豆通报,2005(2):22-24.
[173]Tarnopolsky M A,Parise G, Yardley NJ, et al.Creatine-dextrose and protein-dextrose induce similar strength gain during training[J]. Med Sci Sports Exerc,2001,33(12): 2044-2052.
[174]雷晓妮.不同负荷运动对老龄小鼠骨骼肌组织自由基代谢的影响[D].武汉:武汉体育学院,2007.
[175]Thompson LV, Durand D, Fugere NA, et al. Myosin and actin expression and oxidation in aging muscle[J]. J Appl Physiol,2006 (101):1581-7.
[176]黄彬.运动、机体的抗氧化能力与衰老[J].南京体育学院学报:自然科学版,2003,2(4):8-11.
[177]Bejma J, Ji LL. Aging and acute exercise enhance free redical generation in rat skeletal muscle[J]. J Appl. Physiol,1999(87): 465-70.
[178]Leeuwenburgh C, Fiebig R, Ji LL, et al. Aging and exercise training in skeletal muscle:response of glutathione and antioxidant enzyme systems[J]. Am J Physiol,1994(267):439-445.
[179]邓玉强.运动和大豆多肽对高脂饮食大鼠脂肪肝形成的干预作用及其机制的研究[D].扬州:扬州大学,2007.
[180]Brunk UT, Teman A. Lipofuscin: mechanisms fo age-related accumulation and influence on cell function[J]. Free Radic Biol Med, 2002,33(5):611-9.
[181]Ji LL. Antioxidant enzymes response to exercise and aging[J]. Med.Sci.Sports Exe,1993(25):225-231.
[182]Ji Lili. Exercise and oxidative stress: role of the cellular antioxidant systems. Exercise Sport Science Reviews[M]. edited by Holloszy, J.O. Baltimore, Williams & Wilkins,1995, 135-166.
[183]Burgert TS,Taksali SE,James Dziura,et al. Alanine Aminotransferase Levels and Fatty Liver in Childhood Obesity:Associations with Insulin Resistance,Adiponectin and Visceral Fat[J]. J Clin Endocrinol Metab,2006(91):4287-4294.
[184]Dei R ,Takeda A ,Niwa H,et al. Lipid peroxidation and advanced glycation end products in the brain in normal aging and in Alzheimer’s disease[J]. Acta Neuropathol(Berl),2002,104(2) :113-122.
[185]Ji LL, Wu ED and Thomas DP. Effect of exercise training on antioxidant and metabolic functions in senescent rat skeletal muscle[J]. Gerontology,1991(37): 317-325.
[186]王步标,华明,邓树勋主编.人体生理学[M].北京:高等教育出版社,1994:304-328.
[187]冯连世,李开刚主编.运动员机能评定常用生理生化指标测试方法及应用[M].北京:人民体育出版社,2002:25-36.
[188]Lamberts SW, van den Beld AW, van der Lely AJ. The endocrinology of aging[J]. Science, 1997,278(5337):419-424.
[189]Morley JE, Kaiser FE, Perry HM, et al. Longgitudinal change in testosterone,luteinizing hormone,and follicle-stimulating hormone in healthy older men[J]. Metabolism, 1997, 46(4):412-413.
[190]Seeman TE, Robbins RJ. Aging and hypothalamic-pituitary-adrenal response to challenge in humans[J]. Endocr Rev,1994,15(2):235.
[191]Chen H, Hardy MP, Huhtaniemi I, et al. Age-related decreased Leydig cell testosterone production in the brown Norway rat [J]. J Androl, 1994, 15(5): 551.
[192]金丽.不同强度训练对男子皮划艇运动员血清睾酮水平的影响[J].武汉体育学院学报,2002(2):46.
[193]郑陆.过度训练动物模型的建立[J].中国运动医学杂志,2000,19(2):179-181.
[194]Urhausen A. A 7-week follow up study of behaviour of T and cortisol during the competition period in rowers[J]. Eur J Appl Physiol,1987(56):528-531.
[195]钱风雷.补肾中药对大鼠运动性低血睾酮的调整作用[J].中国运动医学杂志,1998,17(4):320-322.
[196]Yamamoto LM, Lopez RM, Klau JF, et al. The effects of resistance training onendurance distance running performance among highly trained runners: a systematic review[J]. J Strength Cond Res, 2008 ,22(6):2036-2044.
[197]Mandel S,Moreland E,Nichols V,et al. Changes in insuline-like growth factor-1 (IGF-I), IGF-binding protein-3, growth hormonbinding protein, erythrocyte IGF-I receptor, and growth rate during GH treatment[J]. J Clin Endocrinol Metab,1995(80):190-194.
[198]Sundaresan SM, Roemmich JN, Rogol AD. Exercise and developing child: Endocrine considerations.Contemporary endocrindogy: sportsendocrinology[M]. Humana Press Inc. Totowa,NJ 2000. 303-319.
[199]刘广钊,何飞屏,秦晓芬等.甲状腺激素与胰岛素样生长因子-1在衰老中的研究[J].广西医科大学学报,2000, 17(3):371-4.
[200] Nicolas V,Prewett A,Bettica P,et al. Age-related decreases in IGF-I and IGF-B in femoral cortical bone from both men and women implications for bone loss with aging[J]. Clin Endocrinol Metab,1994,78(5):1011.
[201]Kraefner R.Growth hormone,IGF-I and testosterone responses to resistive exercise[J]. Med Sci Sports Exer,1992(24):1346.
[202]Hagberg J M, Seals D R, Yerg J E,et al. Metabolic responses to exercise in young and older athlethes and sedentary men[J]. J Appl Physiol,1988,65 (2):900-908.
[203]Koistinen H,Koistinen R,Selenius L,et al. Effect of marathon run on serum IGF-I and IGF-I and IGF-blinding protein-1 and 3 levels[J]. J Appl Physiol, 1996,80(3):700-704.
[204]Hopkins NJ.Changes in circulating insulin-like growth factor bindingprotein-1 (IGFBP-1)during prolonged exercise:effect of carbohydrate feeding[J]. J Clin Endocrinol Metab,1994(79):1887.
[205]Nicklas B J, Ryan A J, Treuth M M. et al. Testosterone, growth hormone and IGF-I responses to acute and chronic resistive exercisein men aged 55-70 years[J]. Int J Sports Med, 1995,16 (7 ):445-450.
[206] Zanconato,Stefania,David YM,et al.Effect of training and growth hormone suppression on insulin- like growth factor I mRNA in young rat[J]. J.Appl.Phsiol,1994(76): 2204-2209.
[207]Adams, G.R., and F. Haddad. The relationships among IGF-I, DNA content, and proteinaccumulation during skeletal muscle hypertrophy[J]. Journal of Applied Physiology 1996,81(6): 2509-2516.
[208]Taaffe DR.Lack of effect of recombinant growth hormone(rGH)on muscle morphology and GH insulin-like growth factor expression in resistance-trained elderly men[J]. Journal of Clinical Endocrinology and Metabolism,1996(81):421-425.
[209]朱晗,曾凡星.运动对大鼠骨骼肌形态和代谢机能的影响[J].西安体育学院学报,2005,22(2):61-64.
[210]陆耀飞,陆爱云,熊毛弟.短期不同类型跑台训练对大鼠骨骼肌IGF-I基因表达的影响[J].上海体育学院学报,2003,27(5):63-65.
[211]Ranlin W. The effect of oral arginine during energy restriction in male weight trainers[J]. J Strength Condition Res, 1994(8): 170.
[212]Yamaguchi A, Fujikawa T, Tateoka M,et al. The expression of IGF-I and myostatin mRNAs in skeletal muscle of hypophysectomized and underfed rats during postnatal growth [J]. Acts Physiol (Oxf),2006,186(4):291-300.
[213]赵琳.不同强度运动对发育过程中雄性大鼠骨骼肌α-actin mRNA表达的影响[D].北京:北京体育大学,2003.
[214]艾华,陈吉棣,贺师鹏等.大鼠力竭性游泳前后股四头肌α-肌动蛋白基因表达的动态观察[J].中国运动医学杂志,1997,16(2):86-90.
[215]冯连世.优秀中长跑运动员高原训练的生理适应及模拟高原训练时骨骼肌a-actin的基因表达[D].北京:北京体育大学,1998.
[216] Theodore SW. Protein metabolism in rat gastrocnemius muscle after stimulated chronic concentric exercise[J]. J Appl Physiol, 1990, 69(5): 1709-1717.
[217]王瑞元.一次力竭性离心运动后大鼠骨骼肌a-actin代谢、a-actin和MHC基因表达及针刺对其影响[D].北京:北京体育大学,2000.
[218]Kasperek George, Guy J, Conway R, et al. A reexamination of the effect of exercise on rate of muscle protein degradation[J]. Am. J. Physiol, 1992(263):E1144-1150.
[219]Philip B.Clenbuterol prevents or inhibits loss of specific mRNAs in atrophying rat skeletal muscle[J]. Am. J. Phvsiol, 1988,254(Cell Physiol23 ) : 657-660.
[220]赵中应,冯连世,宗丕芳.理气扶正中药消除运动性疲劳过程中骨骼肌α-肌动蛋白基因的表达[J].中国运动医学杂志,1998,17(4): 309-311.
[221]艾华等.锌缺乏对大鼠骨骼肌α-肌动蛋白基因表达的影响[J].营养学报,1996,28(1): 76-80.
[222]Yarasheski KE, Bhasin S, Sinha-Hikim I, et al. Serum myostatin-immunoreactive protein is increased in 60-92 year old women and men with muscle wasting[J]. J Nutr Health Aging, 2002, 6(5):343-348.
[223]Liu W, Thomas S G, Asa S L, et al. Myostatin is a skeletal muscle target of growth hormone anabolic action[J]. Journal of Clinical Endocrinology, 2003(88):5490-5496.
[224]Naomi E. Allen, haul N. Appleby, Rudolf Kaaks, et al. Lifestyle determinants of serum insulin-like growth factor-I(IGF-I),C-peptide and hormone binding protein Levels in British women[J]. Cancer Causes and Control,2003(14):65-74.
[225]Matsakas A, Bozzo C, Caociani N ,et al. Effect of swimming on myostatin expression in white and red gastrocnemius muscle and in cardiac muscle of rats [J]. Exp Physiol,2006,91(6):983-994.
[226]贺道远,曾凡星,朱一力等.急性运动后大鼠骨骼肌Myostatin和IGF-I基因表达呈反向变化[J].体育科学,2008,28(2):54-59.
[227]苏艳红,王瑞元,林华.耐力训练对肌球蛋白重链的影响及MyoD、Myogenin的调控作用[J].体育学刊,2007,14(2):48-52.
[228]Roth SM, Martel GF, Ferrell RE, et al. Myostatin Gene Expression Is Reduced in Humans with Heavy-Resistance Strength Training: A Brief Communication[J]. Exp Biol Med (Maywood), 2003, 228(6):706-709.
[229]McPherron AC, Lee SJ. Suppression of body fat accumulation in myostatin-deficient mice[J]. J Clin Invest, 2002,109:595-601.
[230]Hill JJ, Davis MV, Pearson AA,et al. The myostatin propeptide and the follistatin-related gene are inhibitory binding proteins of myostatin in normal serum[J]. J Biol Chem, 2002(277):40735-40741.
[2]安红梅,胡兵.肾虚衰老理论研究的新思路[J].中国中医基础医学杂志,2004,10(2): 42-44.
[3]许豪文.运动和衰老(上)[J].体育科研,1998,19(2):1-2.
[4]印大中.衰老研究的新纪元[J].生命科学研究,2000, 4(2): 95-101.
[5]刘汴生.衰老的动态变化与抗衰老对策[J].实用老年医学,1998,12(2):73-74.
[6]许豪文.运动生物化学[M].北京:高等教育出版社,2001:346-347.
[7]Vihra BP, Sharma SP, Kansal VK. Age-dependent variations in mitochondrial and cytosolic antioxidant enzymes and lipid peroxidation in different regions of central nervous system of guinea pigs[J]. Indian J Biochem Biophys, 2001,38(5):321-326.
[8]Jang I, JungK, Cho J. Age-related changes in antioxidant enzyme activities in the small intestine and liver from Wistar rats[J]. Exp Anim, 1998,47(4):247-252.
[9]Inal M E,Kanbsk G,Sunal E. Antioxidant enzyme activities and malondialdehyde levels related to aging[J]. Clip Chin Acta , 2001,305(1):75-80.
[10]Wei YH, Lu C Y, Wei C Y, et al. Oxidative stress in human aging and mitochondrial disease-consequences of defective mitochondrial respiration and impaired antioxidant enzyme system[J]. Chin J Physiol, 2001,44(1):1-11.
[11]Kim H C, Bing G Y, Jhoo W K, et al. Oxidative damage causes formation of lipofuscin- like substances in the hippo campus of the senescence-accelerated mouse after kainate treatment[J]. Behav Brain Res, 2002, 131(1-2):211-220.
[12]Gil P, Farinas F, Casado A, et al. Malondialdehyde:a possible marker of ageing[J]. Gerontology, 2002,48(4):209-214.
[13] Stadtman ER. Protein oxidation and aging[J]. Science,1992,257:1220.
[14]龚国清,徐散本.小鼠衰老模型研究[J].中国药科大学学报,1991,22(2):101-103.
[15]马鹤雯,张玉静,阮承迈等.端粒(酶)同癌症与衰老关系的研究进展[J].国外医学·遗传学分册,2000, 23(3): 163-I65.
[16]Martens JW, Sieuwerts AM, Vries JB, et al. Aging of stromal-derived human breast fibroblasts might contribute to breast cancer progression[J]. Thromb Haemost, 2003, 89(2):393-404.
[17]张开红.端粒与端粒酶[J].医学综述,2000, 6(5): 196-199.
[18]Tzukerman M,Selig S,Skorecki K. Telomeres and teloemerase in human health and disease[J]. J Pediatr Endocrinol Metab,2002,15(3):229-240.
[19]杨宇,李发元,胡信群等.衰老小鼠端粒酶活性的测定及意义[J].中国老年学杂志,2002,22(4):266.
[20]Johansson A, Koskiniemi S, Gottfridsson P, et al. Multiple-locus variable-number tandem repeat analysis for typing of Staphylococcus epidermidis[J]. J Clin Microbiol,2006, 44(1):260-265.
[21]Schjeide BM, Hooli B, Parkinson M. GAB2 as an Alzheimer Disease Susceptibility Gene: Follow-up of Genomewide Association Results[J]. Arch Neurol,2009,66(2):250-254.
[22]Stevens JB, Shephered JM, Vories PA,et al. A mixture of mivacurium and rocuronium is comparable in clinical onset to succinylcholine[J]. J Clin Anesth, 1996,8(6):486-90.
[23]马宏,张宗玉,童坦君等.衰老的生物学标志[J].生理科学进展,2002,33(1):65-68.
[24]WangY,MichikawaY,MallidisC,et al. Mussel-specific mutations accumulate with aging in critical human mtDNA control sites for replication[J]. Pros Natl Acad Sci USA,2001,98 (7): 4022-4027.
[25]Harihara S,Nakamura K,Takubo K,et al. Comparison of the level of mitochondrial DAN A3243G mutation in esophageal epithelium and myocardium from individuals of very advanced age[J]. Exp Gerontol,2002,37(7):917-923.
[26]Barazzoni R, Short KR, Nair KS. Effects of aging on mitochondrial DNA copy number and cytochrome c oxidese gene expression in rat skeletal muscle,liver and heart[J]. J Biol Chem,2000,275 (5):3343-7.
[27]Khaidakov M,Heflich RH,Manjanatha MG, et al. Accumulationof point mutations in mitochondrial DNA of aging mace[J]. Muta t Res, 2003,52b(1-2): 1-7.
[28]钱杰,张丽容.衰老小鼠线粒体DNA缺失的研究[J].中国老年学杂志,2003,23(1):43-44.
[29]夏寿萱.放射生物学[M].北京:军事医学出版社,1998.22-44.
[30]崔英俊,李庆章.滑菇多糖对衰老模型鼠不同时期免疫功能的影响[J].东北农业大学学报,2004,35(2):129-134.
[31]陈友琴,胡新珉,刘鸿莲等. YN-PTOL对03衰老模型自由基损伤的保护作用[J].中国医学物理学杂志,2000,17(l):57-58.
[32]董晓华,张丹参,武海霞.衰老动物模型的研究进展及评价[J].河北北方学院学报2004,21(6):41-43.
[33]卫生部.《保健食品功能学检测程序与方法》[S].1996.
[34]赵鹏,杨玉英.半乳糖制备亚急性衰老动物模型的可行性(综述)[J].中国食品卫生杂志,1999,11(1):52-53.
[35]陈勤.抗衰老研究实验方法[M].北京:中国医药科技出版社,1996:46-47.
[36]Ho SC, Liu JH, Wu RY. Establishment of the mimetic aging effect in mice caused by D-galactose[J]. Biogerontology, 2003;4(1):15-8.
[37]徐智,吴国明,钱桂生等.大鼠衰老模型的初步建立[J].第三军医大学学报,2003;25(4): 312-315.
[38]刘晓秋,李卫东,唐惠琼等. D-半乳糖衰老大鼠自由基代谢状况分析[J].中国老年学杂志,2001, 21 (6 ): 456-458.
[39]徐叔云.药理实验方法学[M].北京:人民卫生出版社,2001:1464-1466.
[40]Edstrom E, Altun M, Hagglund M, et al. Atrogin-1/MAFbx and MuRF1 Are Downregulated in Aging-Related Loss of Skeletal Muscle[J]. J Gerontol A Biol Sci Med Sci. 2006,61(7):663-674.
[41]沙继斌.骨骼肌衰老的研究进展[J].山东体育学院学报,2002,18(2):43-46.
[42]邓树勋.运动生理学[M].北京:高等教育出版社,1999:473.
[43]Johnston AP, De Lisio M, Parise G. Resistance training, sarcopenia and the mitochondrial theory of aging[J]. Appl Physiol Nutr Metab,2008 ,33(1):191-199.
[44]ZackerRJ. Health-related implications and management of sarcopenia[J]. JAAPA,2006, 19(10):24-29.
[45]R?ckl KS, Hirshman MF, Brandauer J, et al. Skeletal muscle adaptation to exercisetraining: AMP-activated protein kinase mediates muscle fiber type shift[J]. Diabetes, 2007 ,56(8):2062-2069.
[46]Lytras A, Tolis G. Assessment of endocrine and nutritional status in age-related catabolic states of muscle and bone[J]. Curr Opin Clin Nutr Metab Care,2007,10(5):604-610.
[47]Young A, et al. Size and strength of the quadriceps muscle of old and young women[J]. Eur J Clin Invest, 1984(14): 282-287.
[48]Young A,et al. Ihe size and strength of the quadriceps muscle of old and young men[J]. Clin. Physiol, 1985(5): 145-154.
[49]王润平,任涵.老年体育研究进展[J].西北师范大学学报:自然科学版, 2002,38(1):112-116.
[50]Mcmurdo M and L.Rennier. Improvements in quadriceps strength with regular seated exercise in the institutionalized elderly[J]. Arch. Phys. Med. Rehabil,1994,75:600-603.
[51] Wikipedia网站[OL].http://www.the free encyclopedia.com.
[52]Haus JM, Carrithers JA, Trappe SW,et al. Collagen, cross-linking, and advanced glycation end products in aging human skeletal muscle[J]. J Appl Physiol,2007, 103(6):2068-2076.
[53]Takahashi K, Takahashi HE, Nakadaira H, et al. Different changes of quantity due to aging in the psoas major and quadriceps femoris muscles in women[J]. J Musculoskelet Neuronal Interact,2006,6(2):201-205.
[54]满君.增龄骨骼肌的机能特征及运动对其影响(综述)[J].北京体育大学学报,2001,24(2):200-202.
[55]Synder R J. Effect of testosterone treatment on bodycomposition and muscle strength in men over 65 old years[J]. J. Clin. Endocrinol. Metab,1999,84:2647-2653.
[56]Morles A. J. Effect of replacement dose of dehydroepiandrosterone in men an women of advancing age[J]. J. Clin. Endocrinol. Metab,1994,78:1360-1367.
[57]ButterfieldG.E. Effect of rhGH and rhIGF-I treatmenton protein utilization in elderly women[J]. Am. J. Physiol,1997,272:94-99.
[58]徐秀英,李骁君,王广峰. 6周递增负荷训练对大鼠骨骼肌IGF-I及血清GH—IGF-I水平影响的研究[J].山东体育学院学报,2001,17(4):34-35.
[59]Lunenfeld B, Nieschlag E. Testosterone therapy in the aging male[J]. Aging Male,2007,10(3):139-153.
[60]Machida S, Narusawa M. The roles of satellite cells and hematopoietic stem cells in impaired regeneration of skeletal muscle in old rats[J]. Ann N Y Acad Sci,2006 ,1067:349-353.
[61]Barton-Davis E R. Viral mediated expression of insulin-like growth factorⅠblocks the ageing-related loss of skeletal muscle function[J]. Proc. Natl. Acad. Sci.,1998,95:5603-5607.
[62]Welle S. Growth hormones increases muscle mass and strength but does not rejuvenate myofibrillar protein synthesis in healthy subjects over 60 years old[J]. J. Clin.Endocinol. Metab,1996,81:3239-3243.
[63]Stitt TN, Drujan D, Clarke BA, et al. The IGF-I/PI3K/Akt pathway prevents expression of muscle atrophy-induced ubiquitin ligases by inhibiting FOXO transcription factors [J]. Mol Cell, 2004,14(3):395-403.
[64]Roubenoff R. Origins and Clinical Relevance of Sarcopenia[J]. Canadian Journal of Applied Physiology, 2001.26(1):78-89.
[65]Morley JE, Baumgartner RN, Roubenoff R,et al. Sarcopenia[J]. J Lab Clin Med. 2001,137(4):231-243.
[66]Dupont-Versteegden E E. Apoptosis in muscle at rophy : Relevance to Sarcopenia [J] . Exp Gerontol ,2005 (40) :473-481.
[67]Murlasits Z, Cutlip R G, Geronilla K B, et al. Resistance training increase heat shock protein levels in skeletal muscle of young and old rats[J]. ExpGerontol,2006,41:398-406.
[68]Deschenes MR. Effects of aging on muscle fibre type and size[J]. Sports Med. 2004,34(12):809-824.
[69]牛嗣云.松花粉抗下丘脑-垂体-睾丸衰老机理的实验研究[D].石家庄:河北医科大学,2006.
[70]Paddon-Jones D. Interplay of stress and physical inactivity on muscle loss: nutritional countermeasures[J]. J Nut, 2006 Aug;136(8):2123-2126.
[71]Karakelides H, Nair KS. Sarcopenia of aging and its metabolic impact[J]. Curr Top Dev Biol. 2005(68):123-148.
[72]Geoffrey G,Stephen D R Harridge. Growth factors and muscle aging [J]. Exp Gerontol, 2004(39) :1433-1438.
[73]Goldspin K G. Impairment of IGF-I gene splicing and MGF expression associated with muscle wasting [J]. Int J Biochem Cell Bio ,2006, (38) :481-489.
[74]Sanoudou D, Corbett MA, Han M, et al. Skeletal muscle repair in a mouse model of nemaline myopathy[J]. Hum Mol Genet. 2006,15(17):2603-12.
[75]McNeil CJ, Doherty TJ, Stashuk DW, et al. Motor unit number estimates in the tibialis anterior muscle of young, old, and very old men[J]. MuscleNerve,2005,31(4):461-467.
[76]Susan V. Skeletal muscle weakness in old age:underlying mechanisms[J]. Med. Sci. Sports Exerc,1994,26(4):432-439.
[77]Carlson BM. Muscle transplantation between young and old rats: age of host determines recovery [J]. Am. J.Physiol,1998,256:1262-1266.
[78]Thomas DR. Loss of skeletal muscle mass in aging: examining the relationship of starvation, sarcopenia and cachexia[J]. Clin Nutr. 2007,26(4):389-399.
[79]SharmanMJ,Newton RU,Triplett-McBride T, et al. Changes inmyosin heavy chain composition with heavy resistance training in 60 to 75-year-old men and women[J]. J Appl Physiol,2001,84(1-2):127-132
[80]逄金柱,王瑞元. 2周耐力训练对大鼠骨骼肌肌动蛋白和肌球蛋白重链基因表达的影响[J].中国运动医学杂志,2005 24(4):415-418.
[81]Tajsharghi H, Sunnerhagen KS, Darin N, et al. Induced shift in myosin heavy chain expression in myosin myopathy by endurance training[J]. JNeurol.2004 ,251(2):179-83.
[82]Short KR, Vittone JL, Bigelow ML,et al. human skeletal muscle with age and endurance exercise training[J]. J Appl Physiol,2005,99(1):95-102.
[83]Marx JO, KraemerWJ, Nindl BC,et al. Effects of ging on human skeletal muscle myosin heavy-chain mRNA content and protein isoform expression[J]. J Gerontol A Biol Sci Med Sci,2002,57(6):B232-238.
[84]Vittorio S.Muscle-specific gene expression: a comparison of cardisc and skeletal muscle transcription strategies[J]. Circulation Research, 1993,72(5):925-931.
[85]Joanna Szczepanowska. Effects of denervation and muscle inactivity on organization ofF-actin[J]. Muscle Nerve,1998(21):309-317.
[86]Riley D A.Disproportionate loss of filaments in humansoleus muscle after 17-day bed rest[J].Muscle Nerve,1998,21:1280-1289.
[87] Thomason D B.Altered actin and myosin expression inmuscle during exposure to microgravity[J].J Appl Physiol,1992,73(2):90-93.
[88]McPherron AC, Lawler AM, Lee SJ. Regulation of skeletal muscle mass in mice by a new TGF-βsuperfamily member[J].Nature,1997,387(6628):83-90.
[89]Lee SJ, McPherron AC. Regulation of myostatin activity and muscle growth[J]. Proc Natl Acad Sci USA, 2001,98:9306-9311.
[90]Szabo G, Dallmann G, Muller G, et al. A deletion in the myostatin gene causes the compact (Cmpt) hypermuscular mutation in mice[J]. Mamm Genome, 1998,9:671-672.
[91]Sakuma K, Watanabe K, Sano M, et al. Differential adaptation of growth and differentiation factor 8/myostatin, fibroblast growth factor 6 and leukemia inhibitory factor in overloaded regenerating and denervated rat muscles[J]. Biochim Biophys Acta, 2000(1497):77-88.
[92]高丽,隋波,亓新学等.不同运动方式对后肢固定大鼠腓肠肌肌肉生长抑制素mRNA表达的影响[J].中国运动医学杂志,2008,7;27(4):492-494.
[93]Lalani R, Bhasin S, Byhower F, et al. Myostatin and insulin-like growthfactor-Ⅰand-Ⅱexpression in the muscleof rats exposed to the microgravity environment of the NeuroLab space shuttle flight[J]. J Endocrinol, 2000, 167(3):417-428.
[94]Reardon K A, Davis J, Kapsa R M I et al. Myostatin,insulin-like growth factor-1,and leukemia inhibitory factor mRNAs ere upregulated in chronic human disuse muscle atmphy[J]. Muscle Nerve, 2001, 24, 893-899.
[95]Marcell T J, Harman S M, Urban R J, et al. Comparison of GH, IGF-I, and testosterone with mRNA of receptors and myostatin in skeletal muscle in older men [J]. Am J Physiol Endocrinol Metab, 2001, 281(6):E1159-1164.
[96]Gonzalez-Cadavid NF, Taylor WE, Yarasheski K, et al. Organization of the human myostatin gene and expression in healthy men and HIV-infected men with muscle wasting[J]. Proc Natl Acad Sci U S A,1998 ,95(25):14938-14943.
[97]Yamanouchi K, Soeta C, Naito K, et al. Expression of myostatin gene in regenerating skeletal muscle of the rat and its localization[J]. Biochem Biophys Res Commun, 2000(270):510-516.
[98]Conlon I, Raff M. Size control in animal development[J]. Cell,1999(96):235-244.
[99]Sandri M, Sandri C, Gilbert A, et al. Foxo transcription factors induce the atrophy-related ubiquitin ligase atrogin-1 and cause skeletal muscle atrophy[J]. Cell,2004, 117(3):399-412.
[100]Goldspink G. Loss of muscle strength during aging studied at the gene level[J]. Rejuvenation Res,2007,10(3):397-405.
[101]药立波.医学分子生物学[M].北京:人民卫生出版社,2004:257-262.
[102]陈吉棣.有氧运动、基因表达和慢性病[J ].中国运动医学杂志,2002, 21 (1) : 61-65.
[103]Martin AD, Spenst LF, Drinkwater DT, et al. Anthropometric estimation of muscle mass in men[J]. Med Sci Sports Exerc,1990 ,22(5):729-733.
[104]Fahim MA. Morphological correlates of physiological responses in partially denervated mouse muscle during aging[J]. Int J Dev Neurosci, 1993,11(3):303-310.
[105]Latham N K, Anderson C S, Lee A, et al. A randomized, controlled trial of quadriceps resistance exercise and vitamin D in frail older people : the Frailty Interventions Trial in Elderly Subjects (FITNESS)[J]. Am Geriatr Soc, 2003, 51(4): 291-299.
[106]朱志祥.运动和衰老[J].体育科学,2004,24(7): 37-43.
[107]Visser M, Goodpaster BH, Kritchevsky SB, et al. Muscle mass, muscle strength, and muscle fat infiltration as predictors of incident mobility limitations in well-functioning older persons[J]. J Gerontol A Biol Sci Med Sci,2005,60(3):324-333.
[108]Neil McCartney,et al. A longitud;nal trial of weight training the elderly continued improvements in two years[J]. Journal of Gerontology,1995, 51A(5):425-438.
[109]Sallinen J, Pakarinen A, Fogelholm M, et al. Dietary intake, serum hormones, muscle mass and strength during strength training in 49-73-year-old men[J]. Int J Sports Med,2007,28(12):1070-1076.
[110]Anton MM, Cortez-Cooper M, Devan AE,et al. Resistance Training Increases Basal Limb Blood Flow and Vascular Conductance in Aging Humans[J]. J Appl Physiol,2006101(5):1351-5.
[111]Santtila M, Keijo H, Laura K,et al. Changes in cardiovascular performance during an 8-week military basic training period combined with added endurance or strength training[J]. Mil Med, 2008,173(12):1173-1179.
[112]刘宇,彭千华,田石榴.老年人肌力流失与肌肉疲劳的肌动图研究[J].体育科学,2007,27(5) :57-64.
[113]Salminen A , Vihko V. Effects of age and prolonged running on proteolytic capacity in mouse cardiac and skeletal muscles[J]. Acta Physiol Scared, 1981(112):89- 95.
[114]Proctor D N, Balagopal P, Nair KS. Age-related with re-duced sarcopenia in humans is associated synthetic rated of specific muscle proteins[J]. J Nutr, 1998,(128):5351-5335.
[115]Hayes A, Cribb PJ. Effect of whey protein isolate on strength, body composition and muscle hypertrophy during resistance training[J]. Curr Opin Clin Nutr Metab Care,2008 ,11(1):40-4.
[116]许豪文.运动和衰老(下)[J].体育科研,1998,19(3): 16-21.
[117]李世成.补充大豆肽对一次离心运动后骨骼肌微结构损伤的作用及其机制研究[D].北京:北京体育大学,2004.
[118]赵芳芳.大豆肽的生物学功能研究[D].北京:中国农业大学,2004.
[119]高春霞.大豆多肽生理活性、应用与前景分析[J].大豆通报,2006,(4):18-22.
[120]张美莉主编.食品功能成分的制备及其应用[M].北京:中国轻工业出版社, 2007:117-119.
[121]杨金兰.大豆功能因子的功能作用[J].大豆通报,2005,3:28-29.
[122]陈历俊.大豆活性肽的研制与应用——大豆深加工研究系列之一[D].长春:东北农业大学,1998.
[123]陈晓光,金红梅,胡薇.大豆肽的生理功能及应用前景[J].中国食物与营养,2000(4):39-41.
[124]青山敏明. Recent Advances in the nutritional physiology of soy protein and its peptide[J].食品与开发,1998,7:15-16.
[125]赵秀娟,王小雪等.大豆活性肽粉对饲喂高脂饲料大鼠血脂的影响[J].中国卫生检验杂志,2002,12(4):421-422.
[126]江河源,吕飞杰,邰建祥.大豆种生物活性成分及其功能[J].大豆科学,2000,(19)2:160-161.
[127]崔洪斌.大豆生物活性物质的开发与应用[M ].北京:中国轻工业出版社,2001:257.
[128]高长城,胡锐,李煌馨.大豆肽对增强体能的作用[J].大豆通报,2001(2):24.
[129]Chen H M, Muramoto K, Yamauchi F. Structural analysis of antioxidative peptides form soybean beta-conglycinin[J]. USA: Journal of agricultural and food chemistry,1998. 43(3): 574-578.
[130]张莉莉,王恬.大豆源生物活性肽的研究进展[J].中国油脂,2005,30(4):33-36.
[131]石岗.生物活性肽在动物生产中的应用[J].畜牧与兽医,2002,34(7):38.
[132]Takahiro Tsuruki, Katsuki Kishi, Masakazu Takahashi,et al. Soymetide, an immunostimulating peptide derived from soybean L-conglycinin, is an fMLP agonist[J]. FEBS Letters, 2003(540):206-210.
[133]赵秀娟,吴坤,崔洪斌.大豆活性肽粉的免疫调节作用的试验研究[J].大豆活性物质的研究,2002.
[134]Park MH, Song EY, Ahn C, et al. Two subtypes of hepatitis B virus-associated glomerulonephritis are associated with different HLA-DR2 alleles in Koreans[J]. Tissue Antigens, 2003,62(6):505-511.
[135]Stroescu V, Dragan J, Simionescu L, et al. Hormonal and metabolic response in elite female gymnasts under going strenuous training and supplementation with SUPRO Brand Isolated Soy Protein[J]. J Sports Med Phys Fitness, 2001, 41(1):89-94.
[136]Dr?gan I, Stroescu V, Stoian I,et al. Studies regarding the efficiency of Supro isolated soy protein in Olympic athletes[J]. Rev Roum Physiol,1992,29(3-4):63-70.
[137]中华人民共和国卫生部新闻中心. [OL].http://www.moh.gov.cn/newshtml/20978.htm
[138]荣建华.大豆多肽及其生物活性的研究[D].武汉:华中农业大学,2001.
[139]袁书林,陈海燕,王宵燕等.小肽营养研究进展[J].粮食与饲料工业, 2002(8): 37-39.
[140]孔庆学,甄润英,李玲.大豆蛋白水解物—功能性低聚肽物质的开发研究[J].天津农学院学报, 2002, 9(3): 3-4.
[141]Tohru Fushiki. Effects of the soybean protein on an increase in muscle mass during training in mice[J]. Rep soybean protein Res Com,1994(15):51-56.
[142]魏源.补充活性肽和人参对离心运动后骨骼肌微损伤及其修复效果的观察研究[D].北京:北京体育大学,2005.
[143]王启荣,李肃反,扬则宜,等.补充大豆多肽对中长运动员训练期生化指标的影响[J] .中国运动医学杂志,2004 ,23(1) :33 - 37.
[144]李世成,杨则宜.活性肽及其在运动中的应用[J].中国运动医学杂志, 2003,22(2): 174-176.
[145]林华,于文谦.人体衰老机理及有氧运动对延缓衰老的作用[J].体育学刊, 2000(2);28-30.
[146]贤均.抗衰老研究729篇文献计量分析[J].中国科技期刊研究,1999(1):85.
[147]Morley JE.Weight loss in older persons: new therapeutic approaches[J]. Curr Pharm Des, 2007,13(35):3637-3647.
[148]P?ll?nen E, Ronkainen PH, Suominen H,et al. Muscular transcriptome in postmenopausal women with or without hormone replacement[J]. Rejuvenation Res,2007,10(4):485-500.
[149]Ottenbacher KJ, Ottenbacher ME, Ottenbacher AJ,et al. Androgen treatment and muscle strength in elderly men: A meta-analysis[J]. J Am Geriatr Soc, 2006,54(11):1666-73.
[150]Lee CE, McArdle A, Griffiths RD. The role of hormones, cytokines and heat shock proteins during age-related muscle loss[J]. Clin Nutr, 2007,26(5):524-534.
[151]Brand TC, Canby-Hagino E, Thompson IM. Testosterone replacement therapy and prostate cancer: a word of caution[J]. Curr Urol Rep, 2007,8(3):185-189.
[152]Solomon AM, Bouloux PM.Modifying muscle mass-the endocrine perspective[J]. J Endocrinol, 2006,191(2):349-360.
[153]Wilkinson SB, Phillips SM, Atherton PJ,et al. Differential effects of resistance and endurance exercise in the fed state on signalling molecule phosphorylation and protein synthesis in human muscle[J]. J Physiol, 2008 ,586(15):3701-3717.
[154]Lebrun CE, Schouw YT, de Jong FH,et al. Fat mass rather than muscle strength is the major determinant of physical function and disability in postmenopausal women younger than 75 years of age[J]. Menopause,2006,13(3):474-481.
[155]Nair-Shalliker V, Kee AJ, Joya JE, et al. Myofiber adaptational response to exercise in amouse model of nemaline myopathy[J]. Muscle Nerve,2004 ,30(4):470-480.
[156]Suetta C, Magnusson SP, Beyer N,et al. Effect of strength training on muscle function in elderly hospitalized patients[J]. Scand J Med Sci Sports, 2007 ,17(5):464-472.
[157]Di Iorio A, Abate M, Di Renzo D, et al. Sarcopenia: age-related skeletal muscle changes from determinants to physical disability[J]. Int J ImmunopatholPharmacol,2006,19(4): 703-719.
[158]Bedford TG, Tipion CM, Nilson NC, et al. Maximum oxygen consumption of rats and its changes with various experimental procedure[J]. J Appl Physiol, 1979, 47(6):1278- 1283.
[159]闫万军.负重跑训练改善老龄大鼠肌肉丢失的效果与机理[D].石家庄:河北师范大学,2008.
[160]壄中征哉著.临床肌肉病理学[M].吴士文,马维娅译.北京:人民军医出社,2007:10.
[161]薛红丽,赵佩霞.衰老小鼠皮层NO、MDA、SOD水平变化及其相互关系的研究[J].中国老年学杂志,2000,20(2):89-90.
[162]梁艳菊.四君子汤对D-半乳糖致衰老模型大鼠抗衰老作用的实验研究[D].广州:暨南大学,2005.
[163]沈志祥.运动与衰老[J].体育科学,2004,24(7):37-43.
[164]卫小梅,郭铁成.悬吊运动疗法—一种主动训练及治疗肌肉骨骼疾患的方法[J].中华物理医学与康复杂志,2006,28(4):281-283.
[165]Bradl I, Morl F, Scholle HC, et al. Back muscle activation pattern and spectrum in defined load situations[J]. Pathophysiology, 2005, 12: 275-280.
[166]张保国,王小迪,王安利.本体感觉神经肌肉促进技术治疗大学生一次离心运动后小腿三头肌延迟性肌肉酸痛的效果[J].中国运动医学杂志,2007, 26(6):740-742.
[167]王静.抗阻练习对衰老大鼠骨骼肌中IGF-I, MGF及肌肉生长抑制素的影响[D].上海:华东师范大学,2008.
[168]卢健,陈彩珍,许永刚等.小鼠运动方式——转笼的制作与应用[J].广州体育学院学报,2002,22(5):26-28.
[169]史仍飞,卞玉华,危小焰.振动训练对大鼠骨骼肌质量和肌细胞机械生长因子mRNA表达的影响[J].中国运动医学杂志,2008,27(4):508-510.
[170]Levenhagen D K, Carr C, Carlson MG, et al. Postexercise protein intake enhances whole-body and leg protein accretion in humans[J]. Med Sci Sports Exerc,2002,34(5): 828-837.
[171]Luc J C and Van loon. Ingestion of Protein Hydrolysate and Amino Acid-carbohydrate Mixtures Increases Postexercise Plasma Insulin Responses in Men[J]. J Nutr,2000(130):2508-2513.
[172]陈成.大豆蛋白活性肽保健功能性的研究[J].大豆通报,2005(2):22-24.
[173]Tarnopolsky M A,Parise G, Yardley NJ, et al.Creatine-dextrose and protein-dextrose induce similar strength gain during training[J]. Med Sci Sports Exerc,2001,33(12): 2044-2052.
[174]雷晓妮.不同负荷运动对老龄小鼠骨骼肌组织自由基代谢的影响[D].武汉:武汉体育学院,2007.
[175]Thompson LV, Durand D, Fugere NA, et al. Myosin and actin expression and oxidation in aging muscle[J]. J Appl Physiol,2006 (101):1581-7.
[176]黄彬.运动、机体的抗氧化能力与衰老[J].南京体育学院学报:自然科学版,2003,2(4):8-11.
[177]Bejma J, Ji LL. Aging and acute exercise enhance free redical generation in rat skeletal muscle[J]. J Appl. Physiol,1999(87): 465-70.
[178]Leeuwenburgh C, Fiebig R, Ji LL, et al. Aging and exercise training in skeletal muscle:response of glutathione and antioxidant enzyme systems[J]. Am J Physiol,1994(267):439-445.
[179]邓玉强.运动和大豆多肽对高脂饮食大鼠脂肪肝形成的干预作用及其机制的研究[D].扬州:扬州大学,2007.
[180]Brunk UT, Teman A. Lipofuscin: mechanisms fo age-related accumulation and influence on cell function[J]. Free Radic Biol Med, 2002,33(5):611-9.
[181]Ji LL. Antioxidant enzymes response to exercise and aging[J]. Med.Sci.Sports Exe,1993(25):225-231.
[182]Ji Lili. Exercise and oxidative stress: role of the cellular antioxidant systems. Exercise Sport Science Reviews[M]. edited by Holloszy, J.O. Baltimore, Williams & Wilkins,1995, 135-166.
[183]Burgert TS,Taksali SE,James Dziura,et al. Alanine Aminotransferase Levels and Fatty Liver in Childhood Obesity:Associations with Insulin Resistance,Adiponectin and Visceral Fat[J]. J Clin Endocrinol Metab,2006(91):4287-4294.
[184]Dei R ,Takeda A ,Niwa H,et al. Lipid peroxidation and advanced glycation end products in the brain in normal aging and in Alzheimer’s disease[J]. Acta Neuropathol(Berl),2002,104(2) :113-122.
[185]Ji LL, Wu ED and Thomas DP. Effect of exercise training on antioxidant and metabolic functions in senescent rat skeletal muscle[J]. Gerontology,1991(37): 317-325.
[186]王步标,华明,邓树勋主编.人体生理学[M].北京:高等教育出版社,1994:304-328.
[187]冯连世,李开刚主编.运动员机能评定常用生理生化指标测试方法及应用[M].北京:人民体育出版社,2002:25-36.
[188]Lamberts SW, van den Beld AW, van der Lely AJ. The endocrinology of aging[J]. Science, 1997,278(5337):419-424.
[189]Morley JE, Kaiser FE, Perry HM, et al. Longgitudinal change in testosterone,luteinizing hormone,and follicle-stimulating hormone in healthy older men[J]. Metabolism, 1997, 46(4):412-413.
[190]Seeman TE, Robbins RJ. Aging and hypothalamic-pituitary-adrenal response to challenge in humans[J]. Endocr Rev,1994,15(2):235.
[191]Chen H, Hardy MP, Huhtaniemi I, et al. Age-related decreased Leydig cell testosterone production in the brown Norway rat [J]. J Androl, 1994, 15(5): 551.
[192]金丽.不同强度训练对男子皮划艇运动员血清睾酮水平的影响[J].武汉体育学院学报,2002(2):46.
[193]郑陆.过度训练动物模型的建立[J].中国运动医学杂志,2000,19(2):179-181.
[194]Urhausen A. A 7-week follow up study of behaviour of T and cortisol during the competition period in rowers[J]. Eur J Appl Physiol,1987(56):528-531.
[195]钱风雷.补肾中药对大鼠运动性低血睾酮的调整作用[J].中国运动医学杂志,1998,17(4):320-322.
[196]Yamamoto LM, Lopez RM, Klau JF, et al. The effects of resistance training onendurance distance running performance among highly trained runners: a systematic review[J]. J Strength Cond Res, 2008 ,22(6):2036-2044.
[197]Mandel S,Moreland E,Nichols V,et al. Changes in insuline-like growth factor-1 (IGF-I), IGF-binding protein-3, growth hormonbinding protein, erythrocyte IGF-I receptor, and growth rate during GH treatment[J]. J Clin Endocrinol Metab,1995(80):190-194.
[198]Sundaresan SM, Roemmich JN, Rogol AD. Exercise and developing child: Endocrine considerations.Contemporary endocrindogy: sportsendocrinology[M]. Humana Press Inc. Totowa,NJ 2000. 303-319.
[199]刘广钊,何飞屏,秦晓芬等.甲状腺激素与胰岛素样生长因子-1在衰老中的研究[J].广西医科大学学报,2000, 17(3):371-4.
[200] Nicolas V,Prewett A,Bettica P,et al. Age-related decreases in IGF-I and IGF-B in femoral cortical bone from both men and women implications for bone loss with aging[J]. Clin Endocrinol Metab,1994,78(5):1011.
[201]Kraefner R.Growth hormone,IGF-I and testosterone responses to resistive exercise[J]. Med Sci Sports Exer,1992(24):1346.
[202]Hagberg J M, Seals D R, Yerg J E,et al. Metabolic responses to exercise in young and older athlethes and sedentary men[J]. J Appl Physiol,1988,65 (2):900-908.
[203]Koistinen H,Koistinen R,Selenius L,et al. Effect of marathon run on serum IGF-I and IGF-I and IGF-blinding protein-1 and 3 levels[J]. J Appl Physiol, 1996,80(3):700-704.
[204]Hopkins NJ.Changes in circulating insulin-like growth factor bindingprotein-1 (IGFBP-1)during prolonged exercise:effect of carbohydrate feeding[J]. J Clin Endocrinol Metab,1994(79):1887.
[205]Nicklas B J, Ryan A J, Treuth M M. et al. Testosterone, growth hormone and IGF-I responses to acute and chronic resistive exercisein men aged 55-70 years[J]. Int J Sports Med, 1995,16 (7 ):445-450.
[206] Zanconato,Stefania,David YM,et al.Effect of training and growth hormone suppression on insulin- like growth factor I mRNA in young rat[J]. J.Appl.Phsiol,1994(76): 2204-2209.
[207]Adams, G.R., and F. Haddad. The relationships among IGF-I, DNA content, and proteinaccumulation during skeletal muscle hypertrophy[J]. Journal of Applied Physiology 1996,81(6): 2509-2516.
[208]Taaffe DR.Lack of effect of recombinant growth hormone(rGH)on muscle morphology and GH insulin-like growth factor expression in resistance-trained elderly men[J]. Journal of Clinical Endocrinology and Metabolism,1996(81):421-425.
[209]朱晗,曾凡星.运动对大鼠骨骼肌形态和代谢机能的影响[J].西安体育学院学报,2005,22(2):61-64.
[210]陆耀飞,陆爱云,熊毛弟.短期不同类型跑台训练对大鼠骨骼肌IGF-I基因表达的影响[J].上海体育学院学报,2003,27(5):63-65.
[211]Ranlin W. The effect of oral arginine during energy restriction in male weight trainers[J]. J Strength Condition Res, 1994(8): 170.
[212]Yamaguchi A, Fujikawa T, Tateoka M,et al. The expression of IGF-I and myostatin mRNAs in skeletal muscle of hypophysectomized and underfed rats during postnatal growth [J]. Acts Physiol (Oxf),2006,186(4):291-300.
[213]赵琳.不同强度运动对发育过程中雄性大鼠骨骼肌α-actin mRNA表达的影响[D].北京:北京体育大学,2003.
[214]艾华,陈吉棣,贺师鹏等.大鼠力竭性游泳前后股四头肌α-肌动蛋白基因表达的动态观察[J].中国运动医学杂志,1997,16(2):86-90.
[215]冯连世.优秀中长跑运动员高原训练的生理适应及模拟高原训练时骨骼肌a-actin的基因表达[D].北京:北京体育大学,1998.
[216] Theodore SW. Protein metabolism in rat gastrocnemius muscle after stimulated chronic concentric exercise[J]. J Appl Physiol, 1990, 69(5): 1709-1717.
[217]王瑞元.一次力竭性离心运动后大鼠骨骼肌a-actin代谢、a-actin和MHC基因表达及针刺对其影响[D].北京:北京体育大学,2000.
[218]Kasperek George, Guy J, Conway R, et al. A reexamination of the effect of exercise on rate of muscle protein degradation[J]. Am. J. Physiol, 1992(263):E1144-1150.
[219]Philip B.Clenbuterol prevents or inhibits loss of specific mRNAs in atrophying rat skeletal muscle[J]. Am. J. Phvsiol, 1988,254(Cell Physiol23 ) : 657-660.
[220]赵中应,冯连世,宗丕芳.理气扶正中药消除运动性疲劳过程中骨骼肌α-肌动蛋白基因的表达[J].中国运动医学杂志,1998,17(4): 309-311.
[221]艾华等.锌缺乏对大鼠骨骼肌α-肌动蛋白基因表达的影响[J].营养学报,1996,28(1): 76-80.
[222]Yarasheski KE, Bhasin S, Sinha-Hikim I, et al. Serum myostatin-immunoreactive protein is increased in 60-92 year old women and men with muscle wasting[J]. J Nutr Health Aging, 2002, 6(5):343-348.
[223]Liu W, Thomas S G, Asa S L, et al. Myostatin is a skeletal muscle target of growth hormone anabolic action[J]. Journal of Clinical Endocrinology, 2003(88):5490-5496.
[224]Naomi E. Allen, haul N. Appleby, Rudolf Kaaks, et al. Lifestyle determinants of serum insulin-like growth factor-I(IGF-I),C-peptide and hormone binding protein Levels in British women[J]. Cancer Causes and Control,2003(14):65-74.
[225]Matsakas A, Bozzo C, Caociani N ,et al. Effect of swimming on myostatin expression in white and red gastrocnemius muscle and in cardiac muscle of rats [J]. Exp Physiol,2006,91(6):983-994.
[226]贺道远,曾凡星,朱一力等.急性运动后大鼠骨骼肌Myostatin和IGF-I基因表达呈反向变化[J].体育科学,2008,28(2):54-59.
[227]苏艳红,王瑞元,林华.耐力训练对肌球蛋白重链的影响及MyoD、Myogenin的调控作用[J].体育学刊,2007,14(2):48-52.
[228]Roth SM, Martel GF, Ferrell RE, et al. Myostatin Gene Expression Is Reduced in Humans with Heavy-Resistance Strength Training: A Brief Communication[J]. Exp Biol Med (Maywood), 2003, 228(6):706-709.
[229]McPherron AC, Lee SJ. Suppression of body fat accumulation in myostatin-deficient mice[J]. J Clin Invest, 2002,109:595-601.
[230]Hill JJ, Davis MV, Pearson AA,et al. The myostatin propeptide and the follistatin-related gene are inhibitory binding proteins of myostatin in normal serum[J]. J Biol Chem, 2002(277):40735-40741.
© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号 地址：北京市海淀区学院路29号 邮编：100083 电话：办公室：(+86 10)66554848；文献借阅、咨询服务、科技查新：66554700 |