有氧运动通过激活PI3K(p110α)/Akt信号通路保护2型糖尿病小鼠心功能

Aerobic exercise protects cardiac function of T2DM mice by activation of PI3K(p110α)/Akt signaling pathway

目的:探讨高糖状态下有氧运动对小鼠心功能障碍的作用及相关机制,为糖尿病心功能障碍的运动疗法提供理论和实践依据。方法:将小鼠分成正常非运动组(NNC组)、正常运动组(ENC组)、糖尿病非运动组(NDM组)和糖尿病运动组(EDM组)。实验结束后,评估小鼠的心脏功能,观察心肌组织的病理改变、纤维化情况、ANP的mRNA表达、PI3K(p110α)及Akt的蛋白水平。结果:超声心动图可见糖尿病小鼠心功能降低(P<0.05),运动干预后心功能逐渐恢复(P<0.05)。HE和Masson染色后光镜下可见NDM组小鼠心肌结构极度紊乱,细胞排列不规整,纤维化程度增加,而EDM组心肌受损程度改善。与NNC组相比,糖尿病小鼠心肌组织中ANP的mRNA表达上调,PI3K(p110α)和Akt的蛋白水平受抑制(P<0.05),级联失活。与NDM组相比,EDM组ANP的mRNA降低,PI3K(p110α)和Akt的蛋白水平升高(P<0.01)。结论:糖尿病导致小鼠心肌损害,降低心功能;运动干预可能通过激活PI3K(p110α)/Akt信号通路,缓解高糖导致的心功能障碍,保护心肌细胞。

AIM：To study the protective effect of aerobic exercise on cardiac dysfunction in mice and its mechanism,and to provide theoretical and practical basis for the exercise therapy of diabetic cardiac dysfunction. METHODS：The mice were divided into normal control non-exercise（NNC）group,normal control exercise（ENC）group,diabetic non-exercise（NDM）group and diabetic exercise（EDM）group. At the end of the experiment,the cardiac function was evaluated by echocardiography. The pathological changes of the myocardial tissues and the development of fibrosis were observed. The mRNA expression of ANP,and the protein levels of PI3K（p110α）and Akt were determined. RESULTS：The decrease in cardiac function of diabetic mice was observed,and the cardiac function recovered after exercise intervention（P 〈 0. 05）. Under light microscope with HE and Masson staining,the myocardial structure in NDM group was in extreme disorder,cell arrangement was not neat,and the degree of fibrosis increased,but the myocardial damage was improved in ENC group. Compared with NNC group,the mRNA expression of ANP in the myocardium of diabetic mice was up-regulated（P 〈 0. 05）. The protein levels of PI3K（p110α）and Akt were decreased（P 〈 0. 05）,and the cascade was inactivated. Compared with NDM group,the mRNA expression of ANP was down-regulated and the protein levels of PI3K（p110α）and Akt were up-regulated in EDM group（P 〈 0. 05）. CONCLUSION：Diabetes results in myocardial damage in mice,and reduces cardiac function. Exercise intervention alleviates the heart dysfunction induced by high glucose via activating PI3K（p110α）/Akt signaling pathway to protect the structure and function of the myocardium.