红景天苷对香烟烟雾诱导的慢性阻塞性肺疾病大鼠骨骼肌功能影响的研究
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摘要
目的 研究红景天苷对慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)稳定期模型大鼠骨骼肌的影响。方法 取Wistar大鼠48只,随机分为6组:对照组,对照+红景天苷高剂量组,模型组,模型+红景天苷低、中、高剂量组,每组8只。采用单纯熏烟法复制大鼠COPD模型。红景天连续治疗16周后观察各组大鼠肺功能、肺组织结构,比较肌肉力量、体重及肌肉重量,观察腓肠肌超微结构,测定腓肠肌线粒体复合体Ⅳ(又称细胞色素C氧化酶)活性及线粒体复合体Ⅴ(又称F1F0-ATP合酶)活性。结果 模型组肺功能显著低于对照组,差异有显著性意义,P<0.001;应用红景天苷后,FEV_(0.2)/FVC及PEF较模型组改善,以高剂量组改善最为明显,差异有统计学意义,P<0.001。模型组肺泡腔增大、肺泡壁断裂、肺泡间隔增宽、平均肺泡数较对照组减少,应用红景天苷后,较模型组病理形态明显改善,以高剂量组改善明显。应用红景天苷后,大鼠体重、肌肉重量及肌力较模型组增加,差异有统计学意义(中剂量组,P<0.05,高剂量组,P<0.001)。模型组大鼠腓肠肌细胞线粒体较对照组明显肿胀变性,膜模糊不清,部分破裂,嵴破坏甚至消失,线粒体数量减少甚至消失,形成空泡化,应用红景天苷后由低至高剂量组上述表现逐渐减轻。应用红景天苷后,大鼠腓肠肌组织线粒体细胞色素C氧化酶、ATP合酶活性较模型组逐渐升高,差异均有统计学意义,P<0.001。结论 红景天苷可明显改善COPD模型大鼠肺功能、肌力、体重及肌肉重量,改善腓肠肌线粒体结构,剂量依赖性地升高腓肠肌线粒体细胞色素C氧化酶、ATP合酶活性,从而改善COPD的预后。
Objective To study the effect of salidroside on skeletal muscle function in rats with chronic obstructive pulmonary disease(COPD). Methods 48 Wistar rats were randomly divided into 6 groups: control group, control + high dose salidroside group, model group, model+low, middle and high dose salidroside group, 8 rats in each group.The COPD model in rats was reproduced by smoking alone.For 16 weeks after treatment to observe the lung function and lung tissue structure, muscle strength, body weight and muscle weight, gastrocnemius muscle ultrastructure of each rat, and to determinate the mitochondrial complex Ⅳ(also called cytochrome C oxidase) activity and mitochondrial complex Ⅴ(also called F1 F0 ATP synthase) activity of gastrocnemius muscle. Results The lung function of model group was significantly lower than that of control group(P<0.001). FEV_(0.2)/FVC and PEF were improved after salidroside was applied, especially in high dose group(P<0.001). The alveolar cavity enlargement, alveolar wall rupture, alveolar septum enlargement and average alveolar number in the model group were less than those in the control group. After salidroside was applied, the pathological morphology of the model group was improved significantly, especially in the high dose group. The body weight, muscle weight and muscle strength of salidroside group were significantly higher than those of model group(P<0.05 in middle dose group and P<0.001 in high dose group). Mitochondria of gastrocnemius muscle cells in model group were swollen and degenerated, membranes were blurred, some of them ruptured, cristae was destroyed or even disappeared, mitochondria number was reduced or even disappeared, and vacuolation was formed. After salidroside was applied, the above performance was gradually reduced from low to high dose group. The activities of mitochondrial cytochrome C oxidase and ATP synthase in gastrocnemius muscle tissue of rats after salidroside treatment were higher than those in model group, with statistical significance(P<0.001). Conclusions Salidroside can significantly improve lung function, muscle strength, body weight and muscle weight in COPD model rats, improve mitochondrial structure of gastrocnastus muscle, and increase activities of cytochrome C oxidase and ATP synthase in mitochondria of gastrocnastus muscle dose-dependently, so as to improve the prognosis of COPD.
Objective To study the effect of salidroside on skeletal muscle function in rats with chronic obstructive pulmonary disease(COPD). Methods 48 Wistar rats were randomly divided into 6 groups: control group, control + high dose salidroside group, model group, model+low, middle and high dose salidroside group, 8 rats in each group.The COPD model in rats was reproduced by smoking alone.For 16 weeks after treatment to observe the lung function and lung tissue structure, muscle strength, body weight and muscle weight, gastrocnemius muscle ultrastructure of each rat, and to determinate the mitochondrial complex Ⅳ(also called cytochrome C oxidase) activity and mitochondrial complex Ⅴ(also called F1 F0 ATP synthase) activity of gastrocnemius muscle. Results The lung function of model group was significantly lower than that of control group(P<0.001). FEV_(0.2)/FVC and PEF were improved after salidroside was applied, especially in high dose group(P<0.001). The alveolar cavity enlargement, alveolar wall rupture, alveolar septum enlargement and average alveolar number in the model group were less than those in the control group. After salidroside was applied, the pathological morphology of the model group was improved significantly, especially in the high dose group. The body weight, muscle weight and muscle strength of salidroside group were significantly higher than those of model group(P<0.05 in middle dose group and P<0.001 in high dose group). Mitochondria of gastrocnemius muscle cells in model group were swollen and degenerated, membranes were blurred, some of them ruptured, cristae was destroyed or even disappeared, mitochondria number was reduced or even disappeared, and vacuolation was formed. After salidroside was applied, the above performance was gradually reduced from low to high dose group. The activities of mitochondrial cytochrome C oxidase and ATP synthase in gastrocnemius muscle tissue of rats after salidroside treatment were higher than those in model group, with statistical significance(P<0.001). Conclusions Salidroside can significantly improve lung function, muscle strength, body weight and muscle weight in COPD model rats, improve mitochondrial structure of gastrocnastus muscle, and increase activities of cytochrome C oxidase and ATP synthase in mitochondria of gastrocnastus muscle dose-dependently, so as to improve the prognosis of COPD.
引文
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[10] Gao J,He H,Jiang WJ,et al.Salidroside ameliorates cognitive impairment in a d-galactose-induced rat model of Alzheimer's disease[J].Behav Brain Res,2015,293:27-33.
[11] Chen T,Ma ZQ,Zhu LP,et al.Suppressing receptor-interacting protein 140:a new sight for salidroside to treat cerebral ischemia[J].Mol Neurobiol,2016,53(9):6240-6250.
[12] Zhu LP,Chen T,Chang XY,et al.Salidroside ameliorates arthritis-induced brain cognition deficits by regulating Rho/ROCK/NF-κB pathway[J].Neuropharmacology,2016,103:134-142.
[13] Chen XZ,Wu YP,Yang TH,et al.Salidroside alleviates cachexia symptoms in mouse models of cancer cachexia via activating mTOR signalling[J].J Cachexia Sarcopenia Muscle,2016,7(2):225-232.
[14] Luo F,Liu JY,Yan TH,et al.Salidroside alleviates cigarette smoke-induced COPD in mice[J].Biomed Pharmacother,2017,86:155-161.
[15] Qian EW,Ge DT,Kong SK.Salidroside protects human erythrocytes against hydrogen peroxide-induced apoptosis[J].J Nat Prod,2012,75(4):531-537.
[16] Vézina FA,Cantin AM.Antioxidants and chronic obstructive pulmonary disease[J].Chronic Obstr Pulm Dis,2018,5(4):277-288.
[17] Murǎrescu ED,Iancu R,Mihailovici MS.Morphological changes positive correlates with oxidative stress in COPD.Preliminary data of an experimental rat model:study and literature review[J].Rom J Morphol Embryol,2007,48(1):59-65.
[18] Ottenheijm CA,Heunks LM,Dekhuijzen PN.Diaphragm muscle fiber dysfunction in chronic obstructive pulmonary disease:toward a pathophysiological concept[J].Am J Respir Crit Care Med,2007,175(12):1233-1240.
[19] 王萍,马少林,陈小平,等.慢性阻塞性肺疾病患者膈肌组织形态学变化的研究[J].宁夏医学杂志,2011,33(10):920-922,904.
[2] 胡瑞成,徐永健,张珍祥.吸烟人群的慢性阻塞性肺病易感性[J].国外医学(内科学分册),2003,30(8):346-349.
[3] Kurmi OP,Li LM,Wang J,et al.COPD and its association with smoking in the Mainland China:a cross-sectional analysis of 0.5 million men and women from ten diverse areas[J].Int J Chron Obstruct Pulmon Dis,2015,10:655-665.
[4] Decramer M,Janssens W.Chronic obstructive pulmonary disease and comorbidities[J].Lancet Respir Med,2013,1(1):73-83.
[5] Shi R,Duan J,Deng Y,et al.Nutritional status of an elderly population in Southwest China:a cross-sectional study based on comprehensive geriatric assessment[J].J Nutr Health Aging,2015,19(1):26-32.
[6] Polkey MI,Moxham J.Attacking the disease spiral in chronic obstructive pulmonary disease:an update[J].Clin Med (Lond),2011,11(5):461-464.
[7] Liu GY,He LY.Salidroside attenuates adriamycin-induced focal segmental glomerulosclerosis by inhibiting the hypoxia-inducible factor-1α expression through phosphatidylinositol 3-kinase/protein kinase B pathway[J].Nephron,2019:1-10.
[8] Yang SJ,Yu HY,Kang DY,et al.Antidepressant-like effects of salidroside on olfactory bulbectomy-induced pro-inflammatory cytokine production and hyperactivity of HPA axis in rats[J].Pharmacol Biochem Behav,2014,124:451-457.
[9] Zhu LP,Wei TT,Gao J,et al.The cardioprotective effect of salidroside against myocardial ischemia reperfusion injury in rats by inhibiting apoptosis and inflammation[J].Apoptosis,2015,20(11):1433-1443.
[10] Gao J,He H,Jiang WJ,et al.Salidroside ameliorates cognitive impairment in a d-galactose-induced rat model of Alzheimer's disease[J].Behav Brain Res,2015,293:27-33.
[11] Chen T,Ma ZQ,Zhu LP,et al.Suppressing receptor-interacting protein 140:a new sight for salidroside to treat cerebral ischemia[J].Mol Neurobiol,2016,53(9):6240-6250.
[12] Zhu LP,Chen T,Chang XY,et al.Salidroside ameliorates arthritis-induced brain cognition deficits by regulating Rho/ROCK/NF-κB pathway[J].Neuropharmacology,2016,103:134-142.
[13] Chen XZ,Wu YP,Yang TH,et al.Salidroside alleviates cachexia symptoms in mouse models of cancer cachexia via activating mTOR signalling[J].J Cachexia Sarcopenia Muscle,2016,7(2):225-232.
[14] Luo F,Liu JY,Yan TH,et al.Salidroside alleviates cigarette smoke-induced COPD in mice[J].Biomed Pharmacother,2017,86:155-161.
[15] Qian EW,Ge DT,Kong SK.Salidroside protects human erythrocytes against hydrogen peroxide-induced apoptosis[J].J Nat Prod,2012,75(4):531-537.
[16] Vézina FA,Cantin AM.Antioxidants and chronic obstructive pulmonary disease[J].Chronic Obstr Pulm Dis,2018,5(4):277-288.
[17] Murǎrescu ED,Iancu R,Mihailovici MS.Morphological changes positive correlates with oxidative stress in COPD.Preliminary data of an experimental rat model:study and literature review[J].Rom J Morphol Embryol,2007,48(1):59-65.
[18] Ottenheijm CA,Heunks LM,Dekhuijzen PN.Diaphragm muscle fiber dysfunction in chronic obstructive pulmonary disease:toward a pathophysiological concept[J].Am J Respir Crit Care Med,2007,175(12):1233-1240.
[19] 王萍,马少林,陈小平,等.慢性阻塞性肺疾病患者膈肌组织形态学变化的研究[J].宁夏医学杂志,2011,33(10):920-922,904.