温脾益气化饮方对心梗后心衰大鼠线粒体氧化应激及心室重构的影响OA

Objective This study aimed to investigate the mechanism of mitochondrial oxidative stress in heart failure(HF)after myo-cardial infarction(MI)and the cardioprotective effect of Wenpi Yiqi Huayin Formula(温脾益气化饮方,WYHF).Methods Thirty male Sprague-Dawley(SD)rats underwent left anterior descending coronary artery ligation to establish an MI model.Another 10 rats served as a sham-operated control.The 27 rats that survived surgery and were successfully modeled were randomly divided into the MI model group,the WYHF group,and the sacubitril/valsartan sodium group,with 9 rats per group.Starting on the first day after success-ful modeling,the WYHF group was administered 10.08 g·kg⁻¹ WYHF by gavage,the sacubitril/valsartan group received 0.021 g·kg⁻¹ by gavage,and the sham-operated and model groups received an equal volume of saline.Treatments were administered once daily for 4 weeks.Cardiac structure and function were assessed by echocardiography.Myocardial histopathology and fibrosis were evaluated by HE and Masson staining.Serum ROS and 8-OHdG,as well as myocardial SOD,GSH,and GSH-Px levels,were measured by ELISA.Mitochondrial ultrastructure was examined by transmission electron microscopy(TEM).Mitochondrial membrane potential and mito-chondrial ROS levels in cardiomyocytes were detected using TMRM and MitoSOX Red probes,respectively.The opening of the mito-chondrial permeability transition pore(mPTP)was assessed with the Calcein AM probe.The expression of nuclear factor erythroid 2-related factor 2(Nrf2),superoxide dismutase 2(SOD2),and 8-oxoguanine DNA glycosylase 1(OGG1)in myocardial tissue was evalu-ated by immunohistochemistry(IHC).Western blot(WB)analysis was used to quantify the protein expression of Nrf2,SOD2 and OGG1 in myocardial tissues of each group.Results Compared with the sham-operated group,the model group showed significant increases in left ventricular internal dimension at diastole(LVIDd),left ventricular internal dimension at systole(LVIDs),serum ROS,8-OHdG,and myocardial mitochondrial ROS(mtROS)levels(all P<0.05),along with decreased left ventricular ejection frac-tion(LVEF),left ventricular fractional shortening(LVFS),and myocardial SOD,GSH,GSH-Px,and mitochondrial membrane poten-tial(MMP)levels(all P<0.05).The model group also showed cardiac hypertrophy,marked inflammatory cell infiltration and collagen deposition in the peri-infarct region,abnormal mitochondrial morphology with disrupted cristae and disorganized arrangement,sustained mPTP opening,and reduced myocardial expression of Nrf2,SOD2,and OGG1(all P<0.05).Compared with the model group,WYHF treatment significantly reduced LVIDd,LVIDs,ROS,8-OHdG,and mtROS levels(all P<0.05),and increased LVEF,LVFS,GSH,GSH-Px,and MMP levels(all P<0.05).Furthermore,WYHF attenuated cardiac hypertrophy,improved myocardial histopathology and reduced fibrosis,ameliorated mitochondrial structural damage,limited mPTP opening,and upregulated the myocardial expression of Nrf2,SOD2,and OGG1(all P<0.05).Conclusion WYHF exerts cardioprotective effects in post-MI HF by attenuating mitochon-drial oxidative stress and thereby delaying ventricular remodeling.