摘要
目的:观察慢性低氧及低氧联合运动对骨骼肌线粒体自噬的影响,并探讨低氧诱导因子-1α(HIF-1α)在其中的作用。方法:56只健康雄性SD大鼠随机分为:常氧对照组(NC)、低氧对照组(HC)、低氧联合运动组(HT,n=8)、低氧+二甲基亚砜(DMSO)组(HC+D)、低氧+HIF-1α抑制剂YC-1组(HC+Y)、低氧联合运动+DMSO组(HT+D)和低氧联合运动+HIF-1α抑制剂YC-1组(HT+Y)。低氧干预为常压低氧帐篷,模拟11.3%氧浓度。运动干预为低氧帐篷内53%VO2max跑台训练,1h/d。HIF-1α抑制剂组采用YC-1腹腔注射,4mg/kg,1次/d。DMSO组注射等体积1%DMSO。上述干预均持续4周。结果:HC组与NC组比较,线粒体膜电位、ATP合成活力显著降低(P<0.05),活性氧族(ROS)生成速率、PINK1、Parkin、Bnip3和HIF-1α蛋白表达显著升高(P<0.05)。HT组与HC组比较,线粒体膜电位、ATP合成活力、Parkin、Bnip3和HIF-1α表达显著升高(P<0.05),ROS生成速率和PINK1表达显著降低(P<0.05)。YC-1干预HC和HT组,均造成线粒体膜电位、ATP合成活力、Bnip3和HIF-1α表达显著降低(P<0.05),ROS生成速率和PINK1表达显著升高(P<0.05)。结论:低氧联合运动可通过HIF-1α途径促进了低氧诱导的Bnip3介导的线粒体自噬保护机制,从而提高骨骼肌线粒体的质量。
Objective: To observe the effects of chronic hypoxia alone and hypoxia combined with exercise training on mitochondrial autophagy, and to identify the roles of hypoxia-inducible factor-1α (HIF-1α). Method: A total 56 health male Sprague-Dawley rats were randomly divided into seven groups: normoxia control group (NC), hypoxia control group (HC), hypoxia combined training group (HT), dimethyl sulfoxide(DMSO) injection and hypoxia control group (HC+D), inhibitor of HIF-1α YC-1 injection and hypoxia control group (HC+Y), DMSO injection and hypoxia training group (HT+D), and YC-1 injection and hypoxia training group (HT+Y). The hypoxia rats were subjected to hypoxia exposure in normobaric hypoxic tent. The exercise training rats were administered exercise on a motor-driven rodent treadmill in normobaric hypoxic tent. Rats in HIF-1α inhibitor YC-1 groups received peritoneal injection of the YC-1 DMSO solution at 4mg/kg body weight once a day. Rats in DMSO groups received equivolume injections of the 1% DMSO solution. All interventions were administered for continuous 4 weeks. Result: Comparing with NC group, in HC group, mitochondrial membrane potential and ATP synthesis activity showed dramatic decrease (P〈0.05), and reactive oxygen species(ROS) generation, PINK1, Parkin, Bnip3, HIF-1α protein expression elevated significantly (P〈0.05). Comparing with HC group in HT group, mitochondrial membrane potential, ATP synthesis activity, Parkin, Bnip3, HIF-1α protein expressions improved significantly (P〈0.05), and ROS generation, PINK1 protein expression markedly decreased (P〈0.05). Both in HC and HT rats, YC-1 administration significantly depressed mitochondrial membrane potential, ATP synthesis activity, Bnip3, HIF-1α protein expression (P〈0.05), and markedly elevated ROS generation, PINK1 protein expression (P〈0.05). Conclusion: Hypoxia combined with exercise training could significantly promote hypoxia stress induced mitochondrial autophagy, and then elevated mitochondrial quality. HIF-1α-mediated expression of BNIP3 played an important role in this induction of mitochondrial autophagy.
出处
《中国康复医学杂志》
CAS
CSCD
北大核心
2014年第10期908-912,共5页
Chinese Journal of Rehabilitation Medicine
基金
国家自然科学基金青年基金项目(31200894)
天津市应用基础及前沿技术研究计划青年基金项目(12JCQNJC07900)
关键词
低氧
运动训练
骨骼肌
线粒体自噬
低氧诱导因子α
hypoxia
exercise training
skeletal muscle
mitochondrial autophagy
hypoxia-inducible factor-1α