有氧运动对糖尿病小鼠心肌保护的作用机制及其与微小核糖核酸222的相关性研究

Relationships between aerobic exercise protection mechanism and miRNA-222 in the myocardium of diabetic mice

目的探讨微小核糖核酸222(miR-222)在有氧运动干预后的糖尿病小鼠心肌组织中的表达情况及在心肌保护中的作用。方法将36只小鼠随机分为正常运动组(EC,n=8)、正常非运动组(SC,n=8)、糖尿病运动组(ED,n=10)及糖尿病非运动组(SD,n=10)。造模后给予运动干预,超声测量心功能,光镜下观察心肌组织的病理形态学改变,RT-PCR测定心肌内ANP、β-MHC mRNA及miR-222水平。结果与SC组比较,SD组左室射血分数降低[(74.67±2.05)%vs(66.36±5.08)%,P<0.05],ED组左室射血分数无明显变化(P>0.05);光镜下可见SC、EC组心肌细胞形态规整,排列整齐,SD组心肌细胞结构紊乱,伴炎症细胞浸润,ED组心肌病理结构介于SC和SD之间;SD组心肌内ANP、β-MHC mRNA水平高于其他3组(P<0.05);且运动干预后的EC组、ED组心肌组织内miR-222表达高于相应对照组[(1.53±0.32)vs(0.94±0.14);(1.31±0.32)vs(0.90±0.28),P<0.05]。结论 miR-222的高表达可能参与了有氧运动介导的糖尿病小鼠的心肌保护过程。

Objective To investigate the change of myocardial miR-222 expression after aerobic exercise intervention in diabetic mice and its role in myocardial protection.Methods 36 male C57BL/6mice at the age of 5 weeks were randomly divided into 4 groups：normal exercise group（EC group,n=8）,normal non-exercise group（SC group,n=8）,diabetic exercise group（ED group,n=10） and diabetic nonexercise group（SD group,n=10）.After establishing diabetic model,the mice underwent a 5-week swimming training.The cardiac function of mice was evaluated by echocardiography and the pathological changes of myocardial tissue were observed under light microscope.The levels of ANP,β-MHC,mRNA and miR-222 were measured by real-time fluorescence quantitative PCR（RT-PCR）.Results Compared with SC group,the LVEF of SD group was significantly lower[（74.67±2.05）%vs（66.36±5.08）%,P〈0.05],but no significant reduction in ED group（P〉0.05）.The myocardial cells of SC and EC group were regularly and neatly arranged under the light microscope.The structure of myocardial cells in SD group was disorder,accompanied by inflammatory cell infiltration.The degree of myocardial damage in ED group was between SD and SC group.The levels of ANP and β-MHC mRNA in SD group were significantly higher than the other three groups（P〈0.05）.The expressions of miR-222 in ED and EC group were increased compared with their corresponding control group[（1.53±0.32）vs（0.94±0.14）;（1.31±0.32）vs（0.90±0.28）,P〈0.05].Conclusion High expression of miR-222 may involve in the myocardial protection induced by aerobic exercise in DM mice.