酸枣仁皂苷A调节PINK1/Parkin信号通路介导的线粒体自噬对糖尿病大鼠心肌损伤的影响OA

Objective To investigate the effects and mechanisms of jujuboside A(JuA)on myocardial injury in rats with diabetes mel-litus(DM).Methods Male Sprague-Dawley(SD)rats were divided into the following groups:control,model,metformin,low-and high-dose JuA,and high-dose JuA+Mdivi-1 groups.With the exception of the control group,DM model rats were prepared for all groups.For each group,we assessed cardiac function;examined myocardial pathology and the degree of fibrosis;and measured oxidative stress,autophagy-related indicators,and the expression of PTEN-induced putative kinase 1(PINK1)/Parkin pathway-associated proteins in myo-cardial tissue.Results Compared with rats in the control group,the left ventricular end-diastolic diameter(LVEDd)and left ventricular end-systolic diameter(LVESd),serum creatine kinase-MB(CK-MB)and lactate dehydrogenase(LDH)levels,myocardial tissue collagen volume fraction(CVF),malondialdehyde(MDA)content,and mitochondrial reactive oxygen species(ROS)levels,autophagosome count,and PINK1 protein expression were all higher in the model group rats,whereas left ventricular ejection fraction(LVEF),left ventricular fractional shortening(LVFS),myocardial tissue superoxide dismutase(SOD)activity,and p62 protein levels were decreased(all P<0.05).The addition of metformin and JuA reversed the trends observed for the aforementioned indicators,whereas Mdivi-1 significantly attenu-ated the protective effects of JuA on myocardial injury in DM rats(P<0.05).Conclusion JuA may mediate mitochondrial autophagy by activating the PINK1/Parkin signaling pathway,inhibiting oxidative stress-induced damage in cardiomyocytes,and ameliorating myocar-dial injury in DM rats.