游泳训练通过激活PI3K-Akt信号通路抑制2型糖尿病引起的心肌细胞凋亡

目的:通过建立Wistar大鼠2型糖尿病(T2DM)动物模型,观察T2DM大鼠心肌细胞凋亡及游泳训练对该凋亡事件的保护作用,并探讨其内在影响机制.方法:实验材料Wistar大鼠60只,造模完成后随机分成3组,1)正常对照组(CON)；2) Diabetes模型组(DI)；3)游泳运动组(DI+ SEX),每组15只.游泳训练共计8周.结果:T2DM造成心肌组织Bcl-2水平降低,Bax水平升高；线粒体内及胞浆蛋白中Bax/Bcl-2比值升高,促凋亡物质细胞色素c( Cyt c)向胞浆释放增多(P＜0.01)；糖原合成激酶3β(GSK-3β)磷酸化水平升高(P＜0.05).另外,T2DM引起胰岛素受体亚型1(IR1)水平降低(P＜0.05),失活PI3 K-Akt信号级联.相对地,游泳训练可明显抑制Bax/Bcl-2水平升高及GSK-3β磷酸化水平(P＜0.05),显著性提高PI3K,Akt蛋白磷酸化及胰岛素受体IR1水平(P＜0.05).虽对IR2水平有所提高,但无统计学意义.结论:游泳训练能有效抑制T2DM引起的Wistar大鼠心肌细胞凋亡.其抗凋亡作用可能是通过,至少部分通过上调IR1受体水平,激活PI3K-Akt生存通路,下调其下游关键蛋白CSK-3β磷酸化水平而实现.这表明游泳训练可以有效对抗T2DM引起的细胞凋亡事件的发生.

Swimming Training Inhibits Type 2 Diabetes-Induced Myocardial Apoptosis Activating the PI3K-Akt Signaling Pathway

Purpose:Through establishing diabetes animal model(T2DM),it was observed that T2DM caused myocardial apoptosis and the preservation induced by swimming training,and further the involved anti-apoptosis mechanism is explored.Method:After the model was established,Wistar rats total of 60 were randomly divided into three groups,1)normal control group(CON);2)Diabetes model group(DI);3)Swimming exercise group(DI+SEX),n=15 in each group.Swimming training duration lasted for 8 weeks.Results:T2DM could reduce the contents of Bcl-2,increase Bax levels both in cytoplasm and mitochondria.Rupture of mitochondrial membrane initiated Cytochrome c(Cyt c)and the release into cytoplasm;glycogen synthase kinase 3β(GSK-3β)phosphorylation levels was noteworthy higher than that of other two groups(P<0.05).Meanwhile,the results also showed that insulin receptor subtype 1(IR1)expression was down-regulated(P<0.05)and PI3K-Akt signal cascades were inactivated.Correspondingly,swimming exercise could decline the ratio of Bax/Bcl-2,considerably improve the survival pathway and further activate GSK-3β protein phosphorylation(P<0.05).In addition,swimming exercise also could augment insulin receptor IR1(P<0.05)contents.Although the level of IR2 was enhanced,there is no divergence for statistics.Conclusion:Swim training can effectively inhibit type 2 diabetes-induced myocardial apoptosis in Wistar rats.This anti-apoptotic effect may be through,at least in part,increasing the contents of IR1 receptor,and thereby activate PI3K-Akt signal cascade and further decline the phosphorylation expression of its key downstream of protein-GSK-3β,suggesting that swimming training may be an appropriate modality for combating with myocardial cell damage caused by T2DM.