维康颗粒防治亚健康疲劳的~1H-NMR血清代谢组学研究
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摘要
目的观察中药复方维康颗粒对亚健康疲劳小鼠的干预效应,探讨其防治亚健康疲劳的作用机制。方法10周龄SPF级昆明小鼠30只,根据力竭游泳时间及空腹体质量分层随机分为空白组、模型组及维康颗粒组,每组10只。空白组正常喂养,模型组及维康颗粒组采用将小鼠强迫放入水深为0.8 cm的鼠笼中,每笼1只,每天放置18 h,连续7 d的方式造模。造模期间观察小鼠的行为学表现,造模结束后测试3组小鼠的力竭游泳时间,取腓肠肌行病理学(HE染色)观察及透视电镜检测,取血清行核磁共振氢谱(~1H-NMR)代谢组学检测分析。结果与空白组比较,模型组小鼠精神状态较差,体质量下降(P <0.05),力竭游泳时间缩短(P <0.01),病理学(HE染色)结果未见明显差异,但透视电镜可见线粒体破坏。与模型组比较,维康颗粒组精神状态有改善,体质量无明显变化(P>0.05),但力竭游泳时间显著延长(P <0.05),透视电镜结果示线粒体损伤显著减轻。~1H-NMR血清代谢组学结果显示,亚健康疲劳时血清油脂、不饱和脂肪酸、葡萄糖表达下降,亮氨酸、丙酮酸等12种物质表达上升,而维康颗粒干预后葡萄糖表达上升,丙氨酸、乙酰乙酸等11种物质表达下降,其中葡萄糖、亮氨酸、异亮氨酸、缬氨酸、酮异己酸、丙氨酸、赖氨酸、肌酸、脯氨酸、甘氨酸在干预后表达回调,提示这10种物质可能是维康颗粒干预亚健康疲劳的特异性代谢产物。结论维康颗粒防治亚健康疲劳可能与调整葡萄糖、亮氨酸等血清代谢物的表达,改善能量代谢有关。
Objective To observe the effects of Weikang granule on preventing and treating sub-health fatigue mice,and discuss the mechanism. Methods Thirty male SPF Kunming mice of 10 weeks old were used in this study. All the mice were stratified randomly divide into blank group,model group,Weikang granule group based on their exhausted swimming time(EST) and body weight(BW),10 in each group. The rats in blank group were fed normally;the other two groups were forced into a water cage with a 0.8 cm depth,one mouse per cage,18 h per day,consecutively for 7 days. During the study,behaviors of mice were observed every day. Exhaustive swimming was used to measure the degree of fatigue at the end of the study. Gastrocnemius were observed by the histopathology and electron microscopy, serum was collected for ~1H-NMR research. Results Compared with the blank group,mental state of mice in model group were poorer,BW and EST decreased significantly(P < 0.05). There was no pathological change in histopathology in any group. Electron microscopy showed that the mitochondria were more severely damaged in model and Weikang granule groups. Compared with model group, mental state of Weikang granule group was better;and there was no obvious change of BW between the two groups. EST of Weikang granule group was significantly longer(P < 0.05), mitochondria were less damaged.~1H-NMR results indicate that,compared with blank group,contents of sebum,unsaturated fatty acid and glucose were obviously declined,while levels of other 12 metabolites including leucine,pyruvate were significantly raised in model group. After intervened by Weikang granule,content of glucose was raised while other 11 kinds of metabolites including alanine and acetoacetate were significantly declined. Isoleucine,valine,alanine,leucine,ketoisocaproate,Creatine,proline,glycine and glucose were readjusted after intervention, suggesting that they maybe the special metabolites of Weikang granule on intervening sub-health. Conclusions Weikang granule prevents and treats subhealth fatigue possibly by readjusting the levels of serum metabolites,including glucose,leucine,etc.,and improving the energy metabolism.
Objective To observe the effects of Weikang granule on preventing and treating sub-health fatigue mice,and discuss the mechanism. Methods Thirty male SPF Kunming mice of 10 weeks old were used in this study. All the mice were stratified randomly divide into blank group,model group,Weikang granule group based on their exhausted swimming time(EST) and body weight(BW),10 in each group. The rats in blank group were fed normally;the other two groups were forced into a water cage with a 0.8 cm depth,one mouse per cage,18 h per day,consecutively for 7 days. During the study,behaviors of mice were observed every day. Exhaustive swimming was used to measure the degree of fatigue at the end of the study. Gastrocnemius were observed by the histopathology and electron microscopy, serum was collected for ~1H-NMR research. Results Compared with the blank group,mental state of mice in model group were poorer,BW and EST decreased significantly(P < 0.05). There was no pathological change in histopathology in any group. Electron microscopy showed that the mitochondria were more severely damaged in model and Weikang granule groups. Compared with model group, mental state of Weikang granule group was better;and there was no obvious change of BW between the two groups. EST of Weikang granule group was significantly longer(P < 0.05), mitochondria were less damaged.~1H-NMR results indicate that,compared with blank group,contents of sebum,unsaturated fatty acid and glucose were obviously declined,while levels of other 12 metabolites including leucine,pyruvate were significantly raised in model group. After intervened by Weikang granule,content of glucose was raised while other 11 kinds of metabolites including alanine and acetoacetate were significantly declined. Isoleucine,valine,alanine,leucine,ketoisocaproate,Creatine,proline,glycine and glucose were readjusted after intervention, suggesting that they maybe the special metabolites of Weikang granule on intervening sub-health. Conclusions Weikang granule prevents and treats subhealth fatigue possibly by readjusting the levels of serum metabolites,including glucose,leucine,etc.,and improving the energy metabolism.
引文
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[16]SHI X,XIAO C,WANG Y,et al.Gallic acid intake induces alterations to systems metabolism in rats[J].Journal of Proteome Research,2013,12(2):991-1006.
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[18]孙涛.亚健康学基础[M].北京:中国中医药出版社,2009.
[19]龚云,王超.运动疲劳对大鼠骨骼肌显微结构及糖代谢的影响[J].兰州文理学院学报(自然科学版),2017,31(1):77-81.
[20]聂晓莉,薛琪,罗仁,等.疲劳型亚健康肾阳虚证血浆代谢组学研究[J].中医杂志,2013,54(10):861-864.
[21]查锡良,药立波.生物化学与分子生物学[M].北京:人民卫生出版社,2013.
[22]王一民,郭飞,熊勃,等.杜仲多糖改善运动疲劳的研究[J].中国应用生理学杂志,2016,32(2):151-153.
[2]孙涛,赵晓山,罗仁.亚健康研究的现状与中西医对策[J].中医药管理杂志,2004,14(3):61-62.
[3]CHEN J,CHENG J,LIU Y,et al.Associations between breakfast eating habits and health-promoting lifestyle,suboptimal health status in Southern China:a population based,cross sectional study[J].Journal of Translational Medicine,2014,12(1):1-10.
[4]杨志敏,黄鹂,杨小波,等.亚健康人群的中医体质特点分析[J].广州中医药大学学报,2009,26(6):589-592.
[5]聂晓莉,薛琪,罗仁.疲劳与亚健康的相关性研究[J].热带医学杂志,2010,10(2):145-146.
[6]刘保延,何丽云,谢雁鸣,等.北京地区亚健康人群中医基本证候特征的流行病学研究[J].北京中医药大学学报,2007,30(2):130-135.
[7]孙晓敏,余克强,李玉萍,等.维康颗粒干预亚健康状态的疗效及安全性[J].山东医药,2010,50(25):70-71.
[8]蔡茁,赵晓山,靳文,等.维康颗粒预防大鼠疲劳型亚健康的实验研究[J].广东药学院学报,2009,25(5):504-507.
[9]聂晓莉,薛琪,罗仁,等.维康颗粒对疲劳型亚健康大鼠骨骼肌脂质过氧化和PGC-1α及AMPK表达的影响[J].广东医学,34(11):1654-1656.
[10]刘艳艳,孙晓敏,欧阳明子,等.维康颗粒对疲劳型亚健康小鼠免疫功能影响的实验研究[J].江苏中医药,2013,45(5):73-75.
[11]聂晓莉,薛琪,罗仁,等.维康颗粒对疲劳型亚健康大鼠线粒体再生功能的影响[J].暨南大学学报(自然科学与医学版),2013,34(2):150-153.
[12]HOLLYWOOD K,BRISON D R,GOODACRE R.Metabolomics:Current technologies and future trends[J].Proteomics,2010,6(17):4716-4723.
[13]高鹏飞,刘卫红,吴俊珠,等.代谢组学在中医药研究中的应用进展[J].中国实验方剂学杂志,2011,17(21):284-288.
[14]MCARDLE W D,MONTOYE H J.Reliability of exhaustive swimming in the laboratory rat[J].Journal of Applied Physiology,1966,21(4):1431-1434.
[15]刘艳艳.维康颗粒干预亚健康疲劳的基因表达调控机制研究[D].广州:南方医科大学,2013.
[16]SHI X,XIAO C,WANG Y,et al.Gallic acid intake induces alterations to systems metabolism in rats[J].Journal of Proteome Research,2013,12(2):991-1006.
[17]KIM J,CHOI H J,KWON Y K,et al.1H NMR-Based metabolite profiling ofplasma in a rat model of chronic kidney disease[J].Plos One,2014,9:e854451.
[18]孙涛.亚健康学基础[M].北京:中国中医药出版社,2009.
[19]龚云,王超.运动疲劳对大鼠骨骼肌显微结构及糖代谢的影响[J].兰州文理学院学报(自然科学版),2017,31(1):77-81.
[20]聂晓莉,薛琪,罗仁,等.疲劳型亚健康肾阳虚证血浆代谢组学研究[J].中医杂志,2013,54(10):861-864.
[21]查锡良,药立波.生物化学与分子生物学[M].北京:人民卫生出版社,2013.
[22]王一民,郭飞,熊勃,等.杜仲多糖改善运动疲劳的研究[J].中国应用生理学杂志,2016,32(2):151-153.