耐力训练与p53抑制剂PFT-α对小鼠骨骼肌线粒体自噬相关基因表达的影响  

Effect of Endurance Training and Injection of a p53 Inhibitor PFT-Alpha on Mitophagy in Skeletal Muscle of Mice

作　　者：崔迪[1,2] 贺杰[1,2] 孙婧瑜[1,2] 丁树哲[1,2] 

机构地区：[1]青少年健康评价与运动干预教育部重点实验室,上海200241 [2]华东师范大学体育与健康学院,上海200241

出　　处：《天津体育学院学报》2013年第5期422-426,共5页Journal of Tianjin University of Sport

基　　金：国家自然科学基金项目(项目编号:31171142)

摘　　要：目的:通过6周跑台耐力训练及PFT-α皮下给药干预,探讨耐力训练与PFT-α对小鼠骨骼肌线粒体自噬相关基因表达的影响。方法:8周龄ICR雄性小鼠24只,随机分为对照组C、PFT-α给药组P、耐力训练组E、耐力训练联合PFT-α给药组EP,每组6只;运动组E、EP进行6周跑台训练,P组、EP组皮下注射PFT-α溶液(0.83mg/mLPFT-α,10%DMSO),0.2mL/只/次,C组、E组注射同体积溶剂(10%DMSO)。结果:与C组相比,E组p53、ULK1、BECN1、p62、PINK1、PARK2mRNA表达增加有统计学意义(P<0.05),P组LC3、p62、NIX、BNIP3、PINK1、PARK2、PARLmRNA表达上调有统计学意义(P<0.05),其中,PINK1mRNA的相对含量为C组的12倍;与P组相比,EP组p53、LC3、NIX、BNIP3、PINK1、PARK2mRNA表达下降有统计学意义(P<0.01)。结论:耐力训练可促进PINK1/PARKIN依赖的线粒体自噬相关基因的表达,提示运动对线粒体的质量控制不仅与线粒体生物发生、线粒体动态变化有关,还可能与线粒体自噬有关;PFT-α可促进参与线粒体自噬的NIX/BNIP3信号通路相关基因的表达,提示p53的转录活性与参与线粒体质量控制的NIX/BNIP3信号通路密切相关;PFT-α使PINK1mRNA异常高表达可能导致线粒体功能紊乱,耐力训练可改善这一现象。Objective： 6 weeks of treadmill endurance training and PFT-Alpha subcutaneous injection was taken as interventions to study the effect of endurance training and the injection of PFT-α on mitophagy mechanism in skeletal muscle. Methods： 24 ICR male mice was divided into 4 groups, control group C, endurance training group E, PFT-Alpha injection group P, and the crosstalk of PFT-Alpha injection and endurance training group EP, 6 mice in each group. Endurance training program lasted 6weeks, 6 days per week and 40 minutes each day. PFT-Alpha solution （0.83 mg/mL PFT-Alpha, 10% DMSO） was injected to the mice of group P and EP every two days by 0.2 mL per time, while the equal volume of 10% DMSO solution was injected to the mice of group C and E. Results： Comparing to group C, the relative content of p53, ULK1, BECN1, p62, PINK1, PARK2mRNA increased significantly in the mice of group E（P〈0.05）, while the relative expression of LC3, p62, NIX, B NIP3, PINK1, PARK2, PARLmRNA decreased absolutely in group P （P〈0.05）, in which the mitophagy relevant molecule PINKlmRNA appeared 12 times more than it in the control; comparing to group P, the relative expression of p53, LC3, NIX, BNIP3, PINK1, PARK2mRNA decreased extraordinarily in group EP（P〈0.05）. Conclusions： Endurance training induces the mitophagy in skeletal muscle, which may relay an the PINK1/PARKIN pathway. It implies that the effect of endurance training on Mitochondrial Quality Control is not only related to the Mitochondrial Biogenesis and Mitochondrial Dynamics but also related to the mechanism of Mitophagy. PFT-alpha may activate the NIX/BNIP3 pathway involving in Mitophagy, which suggested that the transcription activity of p53 must have played a critical role in NIX/BNIP3 induced Mitoehondrial Quality Control. The injection of PFT-alpha made PINKlmRNA percussively increase, which may mediate mitochondrial dysfunction, however endurance training can ameliorate this phenomenon.

关 键 词：线粒体自噬 p53 PFT-Α NIX BNIP3 PINK1 PARKIN 

分 类 号：G804.7[文化科学—运动人体科学]