mTOR在有氧运动调节胰岛素抵抗小鼠海马内突触可塑相关蛋白表达中的作用分析

The effect analysis of mTOR in the regulation of aerobic exercise on the expression of synaptic plasticity-related protein in the hippocampus of mice with insulin resistance

目的:探讨有氧运动对胰岛素抵抗小鼠海马内突触可塑相关蛋白表达的影响及可能的mTOR和自噬相关机制。方法:6周龄C57BL/6J雄性小鼠适应性喂养1周后,随机分为普通对照组(C,n=12)和胰岛素抵抗模型组,分别进行普通饲料和高脂饲料喂养12周后,根据GTT、ITT结果判定胰岛素抵抗模型成功建立,并将该组小鼠随机分为胰岛素抵抗安静组(IR,n=10)、胰岛素抵抗+有氧运动组(AE,n=10)。AE组进行为期12周的递增速度跑台训练后,全部小鼠麻醉处死、取脑并剥离出海马组织,利用Western Blot技术检测小鼠海马内胰岛素信号通路,突触可塑、mTOR及自噬相关蛋白的表达情况。结果:胰岛素抵抗小鼠海马内PSD95、SYN的表达及AKT、mTOR的磷酸化水平显著性下降,4EBP2的表达显著性升高。有氧运动可提高mTOR、Raptor、LC3II/LC3I、NMDAR、SYN的表达以及AKT、mTOR的磷酸化水平。结论:有氧运动在提高胰岛素抵抗小鼠海马内PI3K/Akt信号通路活性的情况下,可通过激活mTORC1,进一步提高突触可塑相关蛋白NMDAR、SYN的表达。

Objective:To investigate the effect of aerobic exercise on synaptic plasticity-related protein levels in the hippocampus of mice with insulin resistance and the possible mechanisms of mTOR and autophagy.Method:6-week-old male C57BL/6J mice were randomly divided into normal control group(C,n=12)and insulin resistance model group after a week of adjustable feeding.The mice were maintained for 12 weeks on either normal diet or high-fat diet respectively.According to the date from GTT and ITT to determine the successful establishment of the insulin resistance model.Then the mice with insulin resistance were randomly divided into insulin resistance+quiet group(IR,n=10)and insulin resistance+aerobic exercise group(AE,n=10).Mice in group AE were performed a 12-week increasing speed treadmill training after being adapted to the treadmill for a week.After the intervention,the mice were sacrificed after anesthetized and the brains were collected to get the hippocampus tissue.Insulin signaling pathway,synaptic plasticity-related,mTOR-related and autophagy-related protein expression in the hippocampus of mice with insulin resistance were detected by western blotting.Result:The expressions of PSD95,SYN and the activity of Akt,mTOR decreased significantly,while the expression of 4EBP2 increased significantly in the hippocampus of mice with insulin resistance.Aerobic exercise can effectively improve the expression of mTOR,Raptor,LC3II/LC3I,NMDAR,SYN and the activity of Akt and mTOR.Conclusion:Aerobic exercise can effectively improve the activity of PI3K/Akt signal pathway to active mTORC1,thus improve the expression of NMDAR and SYN in the hippocampus of mice with insulin resistance.