补肺健脾方对COPD大鼠骨骼肌IGF-1、mTOR和HIF1-α的影响

Effects of Bufei Jianpi Formula on Expressions of IGF-1,mTOR and HIF1-α in Skeletal Muscle of COPD Rats

目的:观察补肺健脾方对慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)稳定期模型大鼠股四头肌、肱二头肌、肋间肌、比目鱼肌胰岛素样生长因子(insulin-like growth factor,IGF)^(-1)、哺乳动物雷帕霉素靶蛋白(mammalian target of rapamycin,mTOR)和低氧诱导因子(hypoxia-inducible factor,HIF)^(-1)α表达的影响。方法:48只SD大鼠随机分为空白组、模型组、氨茶碱组、补肺健脾组,每组12只。采用香烟烟雾暴露联合细菌感染法制备COPD稳定期大鼠模型。自第9周起,对照组、模型组给予2 mL生理盐水灌胃;补肺健脾组、氨茶碱组给予补肺健脾方[5 g·(kg·d)^(-1)]、氨茶碱[2.3 m g·(kg·d)^(-1)]治疗,第20周结束后取材。采用荧光定量PCR和Western Blot技术观察4种骨骼肌IGF-1、mTOR和HIF1-αmRNA和蛋白表达。结果:与对照组比较,模型组IGF-1、mTOR mRNA及蛋白表达显著降低(P<0.05),HIF1-αmRNA及蛋白表达显著升高(P<0.01)。与模型组比较,补肺健脾组和氨茶碱组IGF-1、mTOR mRNA表达显著升高(P<0.01),IGF-1、mTOR蛋白表达升高(P<0.05),HIF1-αmRNA和蛋白表达显著降低(P<0.01)。结论:补肺健脾方可通过显著上调IGF-1、mTOR,下调HIF1-α,改善COPD大鼠骨骼肌功能。

Objective：To observe the effects of Bufei Jianpi Formula on the expressions of insulin-like growth factor（IGF）^（-1）,mammalian target of rapamycin（mTOR） and hypoxia-inducible factor（HIF）^（-1）α in quadriceps femoris,biceps brachii,intercostal muscle and soleus muscles in rats with chronic obstructive pulmonary disease（COPD）.Methods：SD rats were randomly divided into control,model,aminophylline and Bufei Jianpi groups.12 rats in each group.COPD rat model was prepared by cigarette smoke exposure combined with bacterial infections.Rats in control and model groups were given 2 mL of saline,while rats in the rest two groups were administrated with Bufei Jianpi Formula [5 g·（kg·d）^（-1）]or aminophylline [2.3 mg·（kg·d）^（-1）],respectively,from week 9 up to 20.Muscle tissues were harvested at week 20.The expressions of IGF-1,mTOR and HIF1-α mRNA and protein in four muscles were observed by using quantitative PCR and Western Blot techniques.Results：IGF-1 and mTOR mRNA and protein in the four muscle were significantly lower in model group than control（P0.05）,while HIF1-α was significantly higher（P0.01）.Compared with model group,IGF-1 and mTOR mRNA and protein was significantly increased in Bufei Jianpi and aminophylline group（P0.01 or P0.05）,while HIF1-α mRNA and protein expression were significantly decreased（P0.01）.Conclusion：Bufei Jianpi Formula can improve skeletal muscle function via up-regulating the expressions of IGF-1,mTOR and depressing HIF1-α.