不同模式低氧训练影响小鼠骨骼肌线粒体自噬与血管生长研究  

Effects of different hypoxic training on the mitophagy and angiogenesis in skeletal muscle of mice

作　　者：赵永才 高炳宏 Zhao Yongcai;Gao Binghong(Tianjin Key Laboratory of Exercise Physiology and Sports Medicine,College of Exercise and Health,Tianjin University of Sport,Tianjin 301617,China;School of Athletic Performance,Shanghai University of Sport,Shanghai 200438,China)

机构地区：[1]天津体育学院运动健康学院运动生理学与运动医学重点实验室,天津301617 [2]上海体育大学竞技运动学院,上海200438

出　　处：《中国运动医学杂志》2024年第7期546-553,共8页Chinese Journal of Sports Medicine

基　　金：国家自然科学基金(31771316)。

摘　　要：目的:探讨运动训练、低氧暴露和不同低氧训练模式对小鼠骨骼肌线粒体自噬及血管生长信号的影响。方法:40只C57BL/6J雄性小鼠随机分5组:对照组(C组)、低氧暴露组(H组)、运动训练组(E组)、高住低练组(LHTL组)及低住高练组(LLTH组),8只/组。H组每天进行8小时低氧暴露(14.8%~12.5%氧浓度);E组每天常氧下进行一次跑台训练;LHTL组结合H组和E组的干预;LLTH组每天进行一次低氧运动;干预6周,5天/周。干预结束后取骨骼肌,冷冻或组织学固定,Western blot测定腓肠肌蛋白,免疫组化评估股四头肌血管内皮生长因子(VEGF)和血小板内皮细胞黏附分子(CD31)表达,透射电镜观察腓肠肌线粒体形态。结果:(1)自噬信号方面,相比C组,LHTL组自噬标记物微管相关蛋白轻链-3Ⅱ/Ⅰ比值(LC3Ⅱ/LC3Ⅰ)显著提高(P<0.01),E组和LHTL组Unc51样自噬激活激酶1磷酸化水平(p-Ulk1)提高(P<0.05)。(2)线粒体自噬信号方面,相比C组,LHTL、LLTH组帕金蛋白(Parkin)和H、LHTL、LLTH组PTEN诱导激酶1(Pink1)蛋白表达均显著提高(P<0.05);E、LHTL及LLTH组BCL2/腺病毒E1B19kda相互作用蛋白3样(Nix)表达显著提高(P<0.05)。其中LHTL组LC3Ⅱ/LC3Ⅰ和Pink1蛋白表达均显著高于E组(P<0.05)。(3)血管信号方面,相比C组,H、E、LHTL、LLTH组骨骼肌VEGF和LHTL、LLTH组CD31表达均显著提高(P<0.05)。电镜观察发现E、LHTL组骨骼肌线粒体体积变大,各组肌原纤维形态正常。结论:低氧训练,尤其高住低练模式明显增强小鼠骨骼肌线粒体自噬信号,并提高血管生长水平,在提升骨骼肌线粒体自噬方面,低氧训练有好于运动训练或低氧暴露的趋势。ObjectiveTo explore the effect of exercise training,hypoxic exposure,and different hypoxic trainings on the mitophagy and angiogenesis in skeletal muscles of mice.MethodsC57BL/6J male mice were randomly divided into a control(C),hypoxic exposure(H),exercise training(E),live high training low(LHTL),and live low training high(LLTH)groups,each of 8.Group H and E were exposed to hypoxia(14.8%~12.5%O2concentration)for 8 h and normoxic exercise in treadmill per day respectively,while group LHTL undertook the both and group LLTH exercised ever day in the hypoxic room for 6 weeks(5 days/week).Skeletal muscle samples were harvested after intervention and then frozen or histologically fixed.Western blotting was used to assess gastrocnemius protein,and immunohistochemistry was employed to evaluate quadriceps angiogenesis.Moreover,the gastrocnemius mitochondria were observed using the transmission electron microscope(TEM).ResultsCompared with group C,the autophagy maker microtubule-associated protein light chain 3Ⅱ/Ⅰprotein ratio(LC3Ⅱ/LC3Ⅰ)of group LHTL and unc51-like autophagy-activating kinase 1 phosphorylation(p-Ulk1)of group E and LHTL increased significantly increased significantly(P<0.01 and P<0.05).Compared with group C,Parkin protein of group LHTL and LLTH,and PTEN induced putative kinase 1(Pink1)protein levels of group H,LHTL and LLTH increased significantly(P<0.05).Moreover,BCL2/adenovirus E1B19Kda protein-interacting protein 3L(Nix)protein levels in group E,LHTL and LLTH increased significantly(P<0.05).In addition,Pink1 protein and LC3Ⅱ/LC3Ⅰlevels of group LHTL were higher than group E(P<0.05).Compared with group C,the skeletal muscle vascular endothelial growth factor(VEGF)levels of group H,E,LHTL and LLTH and cluster of differentiation 31(CD31)level of group LHTL and LLTH also increased significantly(P<0.05).TEM found the mitochondrial volume expansion in group E and LHTL,and the non-injured myofibril in all groups.ConclusionHypoxic training,especially LHTL,upregulating mitophagy and angiogenesis in

关 键 词：运动 骨骼肌 线粒体自噬 血管生成 低氧训练 

分 类 号：G804.2[文化科学—运动人体科学]