钠-葡萄糖协同转运蛋白2抑制剂通过调控沉默信息调节蛋白1/线粒体解偶联蛋白2信号通路对2型糖尿病合并心力衰竭大鼠心功能影响的研究  

The impact of SGLT2 inhibitors on cardiac function in rats with diabetic heart failure through regulation of the SIRTi/UCP2 signaling pathway

作　　者：张沙沙 赵贤淑 刘丽 敖志祥 黄梅 ZHANG Shasha;ZHAO Xianshu;LIU Li(Department of Endocrinology,Yongchuan District People's Hospital,Chongqing 402160,China)

机构地区：[1]重庆市永川区人民医院内分泌科,402160

出　　处：《中国糖尿病杂志》2025年第3期221-226,共6页Chinese Journal of Diabetes

基　　金：永川区自然科学基金计划项目(2022yc-jckx20035)。

摘　　要：目的 探讨SGLT2抑制剂(SGLT2i)通过调控沉默信息调节蛋白1/线粒体解偶联蛋白2(SIRT1/UCP2)信号通路,对T2DM合并心力衰竭(HF)大鼠心功能的影响。方法 40只SD大鼠随机分为正常对照(NC)组、T2DM合并HF(T2DM-HF)组、SGLT2i组和SGLT2i+SIRT1抑制剂(EX527)(SGLT2i+EX527)组。检测各组FBG、心功能和氧化应激指标,HE和Masson染色观察心肌组织病理形态学变化,Western blot法检测心肌组织中SIRT1、UCP2蛋白表达。结果 与NC组比较,T2DM-HF、SGLT2i、SGLT2i+EX527组体重降低(P<0.05),心脏质量指数升高(P<0.05)。与T2DM-HF组比较,SGLT2i组FBG、左心室收缩末期内径(LVESD)、左心室舒张末期内径(LVEDD)、左心室舒张末压(LVEDP)、丙二醛(MDA)、UCP2蛋白表达降低(P<0.05),左心室短轴缩短率(LVFS)、左心室射血分数(LVEF)、左心室最大上升/下降速率(±dp/dtmax)、超氧化物歧化酶(SOD)、SIRT1蛋白表达升高(P<0.05)。与SGLT2i组比较,SGLT2i+EX527组FBG、LVESD、LVEDD、LVEDP、MDA、UCP2蛋白表达升高,LVFS、LVEF、LVSP、±dp/dtmax、SOD、SIRT1蛋白表达降低(P<0.05)。结论 SGLT2i可改善T2DM合并HF大鼠心功能,增强抗氧化能力,对心功能发挥保护作用,其作用机制可能与调控SIRT1/UCP2信号相关通路。Objective To investigate the effect of sodium glucose cotransporter 2 inhibitor(SGLT2i)on cardiac function in T2DM rats with heart failure(HF)by regulating the silencing signaling protein 1/mitochondrial uncoupling protein 2(SIRT1/UCP2)signaling pathway.MethodsForty SD rats were randomly divided into normal control(NC)group,T2DM combined with HF(T2DM-HF)group,SGLT2i group,and SGLT2i+SIRT1 inhibitor(EX527)(SGLT2i+EX527)group.Fasting blood glucose(FBG),cardiac function,and oxidative stress indicators were tested in each group.The pathological morphological changes of myocardial tissue were evaluated by HE and Masson staining,and the expression of SIRT1 and UCP2 proteins in myocardial tissue was evaluated by Western blot.Results Compared with NC group,the T2DM-HF,SGLT2i,and SGLT2i+EX527 groups showed a decrease in body weight(P<0.05)and an increase in cardiac mass index(P<0.05).Compared with T2DM-HF group,the SGLT2i group showed decreased protein expression of FBG,LVESD,LVEDD,LVEDP,MDA,and UCP2(P<0.05),while increased protein expression of LVFS,LVEF,LVSP,±dp/dtmax,SOD,and SIRT1(P<0.05).Compared with SGLT2i group,the SGLT2i+EX527 group showed an increase in FBG,LVESD,LVEDD,LVEDP,MDA,and UCP2 opal levels,while LVFS,LVEF,LVSP,±dp/dtmax,SOD,and SIRT1 opal levels decreased(P<O.O5).Conclusions SGLT2i can improve the cardiac function in T2DM rats combined with HF,enhance antioxidant capacity,and exert a protective effect on cardiac function.Its mechanism of action may be related to the regulation of SIRT1/UCP2 signaling pathway.

关 键 词：钠-葡萄糖协同转运蛋白2抑制剂 糖尿病 2型 心力衰竭 心功能 沉默信息调节蛋白1/线粒体解偶联蛋白2信号通路 

分 类 号：R587.1[医药卫生—内分泌]