1.The impact of SGLT2 inhibitors on cardiac function in rats with diabetic heart failure through regulation of the SIRT1/UCP2 signaling pathway
Shasha ZHANG ; Xianshu ZHAO ; Li LIU ; Zhixiang AO ; Mei HUANG
Chinese Journal of Diabetes 2025;33(3):221-226
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.Methods Forty 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<0.05).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.
2.The impact of SGLT2 inhibitors on cardiac function in rats with diabetic heart failure through regulation of the SIRT1/UCP2 signaling pathway
Shasha ZHANG ; Xianshu ZHAO ; Li LIU ; Zhixiang AO ; Mei HUANG
Chinese Journal of Diabetes 2025;33(3):221-226
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.Methods Forty 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<0.05).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.
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