Mechanism of curcumin ameliorating diabetic cardiomyopathy by modulating the SIRT3/FOXO3a pathway
Objective:To investigate the protective effect of curcumin on mice with diabetic cardiomyopathy and its effect on SIRT3/FOXO3a signaling pathway.Methods:A total of twenty C57BL/6 mice were randomly assigned to four groups,with five mice in each group:the normal control group(Con group),the model group[diabetic cardiomyopathy(DCM)group],the low-dose curcumin group(LC group),and the high-dose curcumin group(HC group).Except for the Con group,the mice in other groups were fed with high-fat and high-glucose diet combined with intraperitoneal injection of streptozotocin(60 mg/kg)to estab-lish the DCM model.After the model was effectively established,the intervention group received high-dose(200 mg∙kg-1∙d-1)and low-dose(100 mg∙kg-1∙d-1)curcumin administration via gavage,while the Con group and DCM group received normal saline ad-ministration via gavage.Following 12 weeks of uninterrupted medication,echocardiography was conducted to assess the myocardi-al structure and function,and HE staining was performed to observe the pathological manifestations of myocardial tissue.The TU-NEL method was utilized to identify apoptosis in mouse cardiomyocytes within each group.The levels of lipid peroxidemalondial,superoxide dismutase,and glutathione peroxidase(GSH-Px)activities in myocardial tissue were assessed,while intracellular ROS levels were measured using DCFH-DA.The expression of mRNA in the SIRT3 and FOXO3a pathways was determined through fluorescence PCR,and the expression of SIRT3,FOXO3a,Bcl2,Bax,and Cleaved caspase-3 proteins was examined using the Western blot method.Results:In comparison to the DCM group,following curcumin intervention,all the indices dem-onstrated amelioration in cardiac ultrasound(P<0.05).TUNEL apoptosis staining revealed a significant reduction in the rate of apoptosis(P<0.05).Additionally,HE staining exhibited notable improvement in cellular edema,disorder in arrangement,the ex-pression of SIRT3,FOXO3a,and Bcl2 was enhanced,while the expression of Bax and Cleaved caspase-3 was diminished.More-over,the activity of superoxide dismutase and GSH-Px exhibited a significant increase(P<0.05),whereas the levels of lipid per-oxidemalondial and ROS were notably decreased(P<0.05).Conclusion:Curcumin has myocardial protective effect and inhibition of ventricular remodeling in mice with diabetic cardiomyopathy,and the mechanism of action may be related to the activation of SIRT3/FOXO3a signaling pathway.
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