有氧运动改善2型糖尿病大鼠股动脉内皮功能障碍的作用及机制

目的:研究规律有氧运动对2型糖尿病大鼠股动脉内皮功能障碍的影响及可能机制。方法:SD大鼠高脂高糖饲养1个月后腹腔注射链脲佐菌素(Streptozotocin,STZ,30mg/kg)制备2型糖尿病大鼠。大鼠分组如下:对照组(Con)、对照运动组(Con-Ex)、2型糖尿病组(type 2 diabetes mellitus,T2DM)、T2DM运动组(T2DM-Ex)。Con-Ex和T2DM-Ex组大鼠进行12周游泳训练。实验开始和结束时,分别测各组大鼠空腹血糖、血浆胰岛素、口服葡萄糖耐量试验(OGTT)曲线下面积(AUCOGTT),计算稳态模型评估胰岛素抵抗指数(HOMAIR)。实验结束后,麻醉大鼠,腹主动脉取血,分离股动脉,检测血浆和股动脉一氧化氮(NO)浓度,离体血管反应性,Western Blot检测股动脉PI3K/Akt/eNOS蛋白表达。结果:实验结束后,与Con组比较,T2DM大鼠空腹血糖、血浆胰岛素、AUCOGTT、HOMA-IR增加(P<0.05),而血浆和股动脉NO含量降低(P<0.05),且对去氧肾上腺素(PE)缩血管反应增加,对乙酰胆碱(ACh)舒血管反应降低(P<0.05),但对硝普钠(SNP)舒血管反应无明显改变。T2DM组大鼠股动脉PI3K,p-Akt和p-eNOS蛋白表达降低(P<0.05)。12周游泳训练显著降低T2DM大鼠血糖、胰岛素、AUCOGTT、HOMA-IR(P<0.05),增加NO水平(P<0.05),降低股动脉对PE缩血管反应,增加对ACh舒张反应(P<0.05),同时增加股动脉PI3K,p-Akt和p-eNO蛋白表达(P<0.05)。结论:有氧运动可通过PI3K/Akt/eNOS/NO通路改善2型糖尿病大鼠股动脉内皮功能障碍。

The ameliorative effect of aerobic exercise on the endothelial dysfunction of femoral artery in type 2 diabetic rats and underlying mechanism

Objective:To investigate the effect and mechanism of aerobic exercise on endothelial dysfunction of femoral artery in type 2 diabetic rats.Method:Type 2 diabetes mellitus SD rats model was established by feeding with high fat and high sugar diet for one month and intraperitoneal injection with streptozotocin(Streptozotocin,STZ,30 mg/kg). Rats were divided into control group(Con), control exercise group(Con-Ex), type 2 diabetes mellitus group(T2DM)and T2DM exercise group(T2DM-Ex). Rats in Con-Ex and T2DM-Ex groups were trained with regular swimming for 12 weeks. At the beginning and end of the experiment,fasting blood glucose,plasma insulin,AUCOGTT and HOMA-IR were measured. At the end of the experiment, the blood was taken from abdominal aorta of anesthetized rats,and the femoral artery was separated. The concentration of nitric oxide(NO) in plasma and femoral artery,vascular reactivity in vitro were tested. The expression of PI3K/Akt/eNOS protein were detected by Western blot.Result:Compared with the Con group,the fasting blood glucose,plasma insulin,AUCOGTT and HOMA-IR in the T2DM rats increased significantly(P<0.05), while the level of NO in plasma and femoral artery decreased(P<0.05). At the same time, the vasoconstrictive response to phenylephrine(PE) increased(P<0.05),the vasodilative response to acetylcholine(ACh) decreased(P<0.05). However, the vasodilative response to sodium nitroprusside(SNP) did not change significantly. The expression of PI3K,p-Akt and p-eNOS reduced in the T2DM rats(P<0.05). Twelve week swimming training significantly reduced fasting blood glucose,plasma insulin,AUCOGTT and HOMA-IR(P<0.05),increased NO level(P<0.05),lowered the contraction of femoral artery to PE and enlarged the relaxation to ACh(P<0.05). Swimming also improved the expression of PI3K,p-Akt and p-eNOS in femoral artery(P<0.05).Conclusion:Aerobic exercise can improve the endothelial dysfunction of femoral artery in T2DM rats through PI3K/Akt/eNOS/NO pathway.