二氢杨梅素对小鼠糖尿病心肌病的保护作用及机制研究

Protective effects and mechanisms of dihydromyricetin on diabetic cardiomyopathy in mice

目的:探究二氢杨梅素(dihydromyricetin,DHY)对小鼠糖尿病心肌病(diabetic cardiomyopathy,DCM)的保护作用及可能机制。方法:C57BL/6小鼠腹腔注射链脲佐菌素(streptozotocin,STZ)60 mg/(kg·d^(-1)),连续5 d,构建小鼠糖尿病模型。2周后给予DHY 250 mg/(kg·d^(-1))灌胃,期间每2周定期监测小鼠空腹血糖。12周后测定糖化血红蛋白(glycosylated hemoglobin,HbA1c)含量,超声心动图评估心功能,检测心肌组织丙二醛(malondialdehyde,MDA)水平和总抗氧化能力(total antioxidant capacity,T-AOC),蛋白印迹检测心肌组织中去乙酰化酶3(sirtuin 3,SIRT3)和受体相互作用蛋白激酶3(receptor interacting protein kinase 3,RIPK3)蛋白表达。结果:DHY降低STZ诱导小鼠的空腹血糖浓度和HbA1c水平,增加射血分数、短轴缩短率和心室舒张期E峰和A峰血流比值,抑制MDA水平,增强T-AOC,上调SIRT3表达,下调RIPK3表达。结论:DHY增加糖尿病小鼠心肌组织中SIRT3表达,抑制氧化应激,减弱坏死性凋亡,增强心脏收缩和舒张功能,减轻DCM损伤。

Objective:To investigate the effects and possible mechanisms of dihydromyricetin(DHY)on diabetic cardiomyopathy(DCM)in mice.Methods:C57BL/6 mice were intraperitoneally injected with streptozotocin(STZ)60 mg/(kg·d^(-1))for 5 consecutive days to establish the diabetic model.After 2 weeks,DHY 250 mg/(kg·d^(-1))was administrated by gavage.Fasting blood glucose was monitored every 2 weeks.After 12 weeks,glycosylated hemoglobin(HbA1c)level was measured.Cardiac function was evaluated by echocardiography.Myocardial malondialdehyde(MDA)level and total antioxidant capacity(T-AOC)were measured.The protein expression of sirtuin 3(SITR3)and receptor interacting protein kinase 3(RIPK3)in the myocardium were detected by Western Blot.Results:DHY treatment reduced fasting blood glucose concentration and HbA1c level,enhanced ejection fraction,fraction shortening and the ratio of peak E to peak A in ventricular diastolic phase,suppressed MDA level,increased T-AOC,up-regulated SIRT3 but down-regulated RIPK3 expression in mice with DCM.Conclusion:DHY increased SIRT3 expression,inhibited oxidative stress,alleviated myocardial necroptosis,enhanced cardiac systolic and diastolic function,and attenuated damage in DCM.