AMPK/PGC-1α在有氧运动改善2型糖尿病大鼠骨骼肌萎缩中的作用

Effect of AMPK/PGC1 alpha on improving skeletal muscle atrophy in type 2 diabetic rats by aerobic exercise

背景:腺苷酸活化蛋白激酶(AMP-activated kinase,AMPK)对线粒体能量代谢功能的调节障碍是导致肥胖和2型糖尿病患者脂肪堆积的重要原因,长期慢性炎症反应还将进一步诱导骨骼肌萎缩的发生,有氧运动可以提高AMPK的活性并调节能量代谢,但是通过有氧运动提高AMPK改善2型糖尿病骨骼肌萎缩的作用机制尚不明确。目的:探究有氧运动对2型糖尿病大鼠骨骼肌萎缩的影响,以及AMPK在其中的作用机制。方法:采用高脂饲养联合链脲佐菌素注射建立2型糖尿病大鼠模型20只,建模后将大鼠分为糖尿病组(n=8)和糖尿病运动组(n=12),同时将正常大鼠15只分为安静对照组(n=6)和运动组(n=9),其中安静对照组和糖尿病组继续饲养4周,运动组和糖尿病运动组进行有4周有氧运动干预(跑速16 m/min,60 min/d,5 d/周),运动干预后取大鼠比目鱼肌免疫组织化学染色观察各组肌萎缩情况,Western blot检测AMPK、PGC-1α、MAFbx和MuRF1蛋白表达情况。实验已于2016-06-25通过北京体育大学运动科学实验伦理委员会批准(批准号:2016014)。结果与结论:①高脂饲养联合链脲佐菌素注射建立的2型糖尿病模型大鼠血糖显著升高、体质量和胰岛素水平显著下降(P<0.01);②糖尿病组大鼠比目鱼肌肌纤维平均横截面积较安静对照组显著降低(P<0.01),糖尿病运动组大鼠比目鱼肌肌纤维平均横截面积较糖尿病组显著升高(P<0.01);③糖尿病组大鼠比目鱼肌中AMPK和PGC-1α表达水平较安静对照组显著降低,MAFbx和MuRF1表达水平较安静对照组显著升高(P<0.01);糖尿病运动组大鼠AMPK表达水平较糖尿病组显著升高,MAFbx和MuRF1的水平较糖尿病组显著降低(P<0.01);④上述结果说明,有氧运动通过激活AMPK/PGC-1α信号通路,提高线粒体功能,抑制MAFbx和MuRF1表达水平,改善骨骼肌萎缩,在一定程度上恢复了2型糖尿病的代谢平衡。

BACKGROUND:The regulation of mitochondrial energy metabolism by adenylate activated protein kinase(AMPK)is an important cause of fat accumulation in obese and type 2 diabetic patients.Chronic inflammation will further induce skeletal muscle atrophy.Aerobic exercise can increase the activity of AMPK and regulate energy metabolism,but the mechanism of aerobic exercise in improving skeletal muscle atrophy in type 2 diabetes by increasing AMPK is unclear.OBJECTIVE:To explore the effect of aerobic exercise on skeletal muscle atrophy in type 2 diabetic rats and the role of AMPK.METHODS:The model of type 2 diabetic rats was established by high fat feeding and streptozotocin injection,and the rats were divided into four groups:control group(n=6),exercise group(n=9),diabetic control group(n=8)and diabetic exercise group(n=12).The control group and the diabetic control group were kept for 4 weeks,and the exercise group and the diabetic exercise group were given aerobic exercise intervention for 4 weeks.After 4 weeks of aerobic exercise(running speed 16 m/min,60 min/d,5 days/week),the muscle atrophy of soleus was observed by immunohistochemical staining.The expression levels of AMPK,PGC-1α,MAFbx and MuRF1 were detected by western blot assay.The study protocol was approved by the Ethical Committee of School of Sport Science,Beijing Sport University in China on June 25,2016,with approval No.2016014.RESULTS AND CONCLUSION:Blood glucose of type 2 diabetes rats was significantly increased,and body weight and insulin levels of type 2 diabetes rats were significantly decreased(P<0.01).The mean cross sectional area of soleus fiber in the diabetic group was significantly lower than that in the control group(P<0.01),and the cross sectional area of soleus muscle fiber in the diabetic exercise group was significantly higher than that in the diabetic group(P<0.01).The expression levels of AMPK and PGC-1αin the soleus muscle of diabetic rats were significantly lower than those in the control group,and the expression levels of MAFbx and MuRF1 were significantly higher than those in the control group(P<0.01).The expression levels of AMPK,MAFbx and MuRF1 in the diabetic exercise group were significantly higher than those in the diabetic group(P<0.01).These results suggest that aerobic exercise can improve mitochondrial function,inhibit the expression of MAFbx and MuRF1,improve skeletal muscle atrophy and restore the metabolic balance of type 2 diabetes mellitus to some extent by activating AMPK/PGC-1αsignaling pathway.