mTOR在运动干预高脂膳食大鼠胰岛素抵抗形成中的作用及机制研究

Effect of m TOR on the generation of insulin resistance of exercise inducing the high-fat diet rats

目的:探讨哺乳动物雷帕霉素靶蛋白(m TOR)在高脂膳食诱导胰岛素抵抗(IR)的形成及运动干预中的作用。方法:选用清洁级的雄性SD大鼠40只,随机分为4组:正常对照组(C组,n=10);高脂膳食组(H,n=10);游泳运动组(E,n=10);高脂膳食+游泳运动组(HE,n=10)。按实验要求分别给予普通饲料和高脂饲料,E、HE组每天无负重游泳运动1小时。11周后检测各组大鼠空腹血糖(FBG)、血清胰岛素(FBG)、骨骼肌AMPK、PI3K、Akt、m TOR、S6K1的表达量。结果:1)与C组相比,H组FBG、FINS、胰岛素抵抗指数(HOMA-IR)均显著性升高(P<0.01)(P<0.05),E组FINS极显著性下降(P<0.01);与H组相比,HE组FINS显著性下降(P<0.05)。2)与C组比较,H组骨骼肌m TOR含量和mRNA都有显著性增加(P<0.05),S6K1mRNA极显著性升高(P<0.01);与H组比较,HE组骨骼肌m TOR、S6K1mRNA显著性减少(P<0.05)。3)与C组比较,E组骨骼肌Akt和AMPK含量显著性增加(P<0.01);与H组比较,HE组骨骼肌PI3K、Akt、AMPK含量有增加,但均无显著性(P>0.05)。结论:1)长期的高脂膳食可激活m TOR/S6K1信号通路,导致胰岛素抵抗的发生。2)有氧运动激活AMPK,抑制m TOR的作用,AMPK/m TOR/S6K1可能在运动干预高脂膳食诱导IR形成中起着重要的作用。

Objective：Explore the effect of mTOR on the generation of insulin resistance of high-fat diet and exercise induced.Methods：40 Sprague-Dawley（SD）male rats were randomly divided into control group（C,n=10）,High-Fat Diet Rats（H,n=10）,Swimming Exercise Rats（E,n=10）and High-Fat Diet＋Swimming Exercise Rats（HE,n =10）.According to the acquirement,they should be fed separately normal diet and high-fat diet.Rats in group E and group HE were both asked to swim for one hour with non-weight bearing everyday.After 11weeks,measuring the content of FBG,FINS,the expression of AMPK,PI3K,Akt,mTOR,S6K1 in skeletal muscles.Results：1）Compared with group C,the FBG,FINS and the HOMA-IR of group H had both increased significantly（P〈0.01）（P〈0. 05）,the FINS of group E had decreased significantly（P〈0.01）;Compared with group H,the FINS of group HE had decreased significantly （P 〈0.05 ）.2 ）Compared with group C,the content of mTOR,the mRNA of mTOR and S6K1 of group H had increased significantly（P〈0.05,P〈0.01）. Compared with group H,the mRNA of mTOR and S6 K1 of group HE had decreased significantly（P〈0.05）.3）Compared with group C,the AMPK and Akt content of group E had decreased signifi-cantly（P〈0.01）.Compared with group H,the content of PI3K,Akt and AMPK of group HE had no significant difference（P〉0.05 ）.Conclusion：1 ）Long-time High -fat diet activated the mTOR/S6K1 signalway,which induced insulin resistance.2 ）Exercise activated AMPK while in return AMPK restrained the mTOR,AMPK/mTOR/S6 K1 might be very important for exercise to intervene insulin resistance.