大黄酸通过调控Sirt1/PGC⁃1α通路对糖尿病心肌病的改善作用及机制研究

The protective effect and mechanism of rhein on diabetic cardiomyopathy by regulating Sirt1/PGC⁃1αpathway

目的:探讨大黄酸对糖尿病心肌病的保护作用及其可能机制。方法:采用腹腔注射链脲佐菌素联合高脂饮食构建糖尿病小鼠模型,随机分为对照组、糖尿病组、糖尿病+大黄酸组。大黄酸干预12周后,观察小鼠空腹血糖、体重、心脏/体重比值变化;HE、Masson染色观察心肌结构;透射电子显微镜观察心肌线粒体结构;实时荧光定量PCR检测心肌组织中Sirt1、PGC‑1α、TFAM、ANP、BNP和β‑MHC mRNA表达;Western blot、IHC检测Sirt1、PGC‑1α、TFAM蛋白表达。结果:与对照组比,糖尿病组小鼠血糖、心脏/体重比值、心肌ANP、BNP和β‑MHC mRNA明显增加(P<0.05);心肌及线粒体结构明显破坏;心肌Sirt1、PGC‑1α、TFAM表达明显降低(P<0.05);与糖尿病组相比,大黄酸干预后小鼠血糖、心脏/体重比值、ANP、BNP和β‑MHC mRNA表达降低(P<0.05);心肌及线粒体损伤减轻;Sirt1、PGC‑1α、TFAM表达明显增加(P<0.05)。结论:大黄酸对糖尿病心肌损伤具有保护作用,其机制之一可能是通过激活Sirt1/PGC‑1α信号通路实现的。

Objective:To explore the protective effects of rhein on cardiomyocyte injury in DCM and its possible mecha-nism.Methods:The diabetic model was induced by intraperitoneal injection with streptozotocin and high-fat diet.The mice were randomly divided into control group,DM group,and DM+RH group.After 12 weeks treatment with rhein,the change of fast blood glucose,body weight,and heart weight/body weight(HW/BW)were observed.HE and Masson staining were used to evalu-ate myocardial structural damage.Transmission electron microscope was used to observe the myocardial mitochondrial structure.The mRNA levels of Sirt1,PGC-1α,TFAM,ANP,BNP andβ-MHC were quantified by RT-PCR.Sirt1,PGC-1αand TFAM protein levels were estimated by Western blot and IHC.Results:Compared with control group,the blood glucose,HW/BW,ANP,BNP andβ-MHC mRNA of DM group were significantly increased(P<0.05).The structures of myocardium and mitochon-dria were obviously destroyed in DM group.Sirt1,PGC-1αand TFAM expression were significantly decreased(P<0.05).Com-pared with DM group,the blood glucose,HW/BW,ANP,BNP andβ-MHC mRNA of DM+RH group were decreased(P<0.05).The myocardial and mitochondrial injury were improved.Sirt1,PGC-1αand TFAM expression were significantly increased(P<0.05).Conclusion:Rhein exhibits protective effects on diabetic cardiomyopathy which may be achieved by activating Sirt1/PGC-1αpathway.