白藜芦醇对慢性阻塞性肺疾病大鼠骨骼肌过氧化物酶增殖物激活受体因子γ辅激活因子-1α表达的影响

Effect of resveratrol on the expression of peroxisome proliferator activated receptor γ coactivator-1α in skeletal muscle of rats with chronic obstructive pulmonary disease

目的探讨白藜芦醇对慢性阻塞性肺疾病(COPD)大鼠骨骼肌过氧化物酶增殖物激活受体因子γ辅激活因子-1α(PGC-1α)表达的影响。方法将45只雄性Sprague Dawley大鼠随机分为对照组、模型组和白藜芦醇组,每组15只。除对照组外,模型组和白藜芦醇组大鼠通过气管内滴注脂多糖和反复烟雾暴露法构建COPD模型。自烟雾暴露第29天起,对照组和模型组大鼠给予2 m L生理盐水灌胃,每日1次,连续灌胃30 d;白藜芦醇组大鼠给予2 m L白藜芦醇溶液灌胃(100 mg·kg-1·d-1),每日1次,连续灌胃30 d。灌胃30 d后处死大鼠,取动脉血及小腿骨骼肌。采用酶联免疫吸附试验测大鼠血清和小腿骨骼肌中肿瘤坏死因子-α(TNF-α)水平,实时荧光定量聚合酶链反应测各组大鼠骨骼肌组织中PGC-1α、核呼吸因子1(NRF1)、线粒体转录因子A(Tfam)、细胞色素C氧化酶Ⅳ(COXⅣ)mRNA表达,Western blot测各组大鼠骨骼肌组织中PGC-1α、NRF1、Tfam、COXⅣ蛋白表达。结果模型组和白藜芦醇组大鼠血清和骨骼肌组织中TNF-α水平显著高于对照组(P<0.01),白藜芦醇组大鼠血清和骨骼肌组织中TNF-α水平显著低于模型组(P<0.01)。白藜芦醇组和模型组大鼠骨骼肌组织中PGC-1α、NRF1、Tfam、COXⅣ蛋白及mRNA表达显著低于对照组(P<0.01);白藜芦醇组大鼠骨骼肌组织中PGC-1α、NRF1、Tfam、COXⅣ蛋白及mRNA表达显著高于模型组(P<0.01,P<0.05)。结论白藜芦醇可以降低COPD大鼠血清及骨骼肌组织中TNF-α水平,提高PGC-1α表达水平,从而改善线粒体的生物合成功能。

Objective To investigate the effect of resveratrol on the expression of peroxisome proliferator activated receptor γ coactivator-1α（PGC-1α） in skeletal muscle of rats with chronic obstructive pulmonary disease（COPD）. Methods A total of 45 male Sprague Dawley rats were randomly divided into control group,model group and resveratrol group,15 rats in each group. The rats in the model group and resveratrol group were made COPD model through the intratracheal instillation of lipopolysaccharide and repeated smoke exposure,except the rats in the control group. From the 29 thday of smoke exposure,the rats in the control group and model group were given 2 m L saline by gavage,once a day for 30 days; and the rats in the resveratrol group were given 2 m L resveratrol solution by gavage（100 mg·kg-1·d-1）,once a day for 30 days. After 30 days of continuous gavage,the rats were sacrificed,then arterial blood and skeletal muscles were harvested. The level of tumor necrosis factor-α（TNF-α） in serum and skeletal muscle of rats was detected by enzyme linked immunosorbent assay. The expression of PGC-1α,nuclear respiratory factor 1（NRF1）,mitochondrial transcription factor A（Tfam） and cytochrome C oxidase Ⅳ（COXⅣ） mRNA in skeletal muscle tissues of rats was determined by quantitative real-time polymerase chain reaction. The expression of PGC-1α,NRF1,Tfam and COX Ⅳ protein was detected by Western blot. Results The level of TNF-α in serum and skeletal muscle tissues of rats in the model group and resveratrol group was significantly higher than that in the control group（P〈0. 01）. The level of TNF-α in serum and skeletal muscle tissues of rats in the resveratrol group was significantly lower than that in the model group（P〈0. 01）. The expression of PGC-1α,NRF1,Tfam,COX Ⅳ protein and mRNA in skeletal muscle tissues of rats in the resveratrol group and model group was significantly lower than that in the control group（P〈0. 01）.The expression of PGC-1α,NRF1,Tfam,COX Ⅳ protein and mRNA in skeletal muscle tissues of rats in the resveratrol group was significantly higher than that in the model group（P〈0. 01,P〈0. 05）. Conclusion Resveratrol can reduce the level of TNF-α in serum and skeletal muscle tissues of COPD rats,increase the expression of PGC-1α,thereby improving the mitochondrial biosynthesis function.