参芪健心方抑制内质网应激改善心力衰竭大鼠心功能OA

Objective To evaluate the therapeutic efficacy of Shenqi Jianxin Formula(SQJXF)in heart failure(HF)and to investigate whether its cardioprotective effects involve modulation of sialyltransferase 7A(Siat7A)and the endoplasmic reticulum(ER)chaperone glucose-regulated protein 78(GRP78),thereby attenuating endoplasmic reticulum stress(ERS).Methods A rat model of HF was established via abdominal aortic constriction.Twenty-four successfully modeled rats were randomly divided to four groups(6 rats in each group):HF model,SQJXF high-dose and low-dose groups(17.64,4.41 g·kg-1·d-1),and sacubitril/valsartan sodium group(10 mg·kg-1·d-1).An additional six rats underwent sham surgery without vascular constriction.All interventions were administered by oral gavage for 4 weeks.Cardiac function was assessed by echocardiography.Serum levels of atrial natriuretic peptide(ANP)and B-type natriuretic peptide(BNP)were quantified using ELISA.Histopathological alterations and myocardial fibrosis were evaluated by hematoxylin-eosin(HE)and Masson's trichrome staining.Expression levels of Siat7A and GRP78 mRNA and protein were determined using RT-qPCR,Western Blot,and immunohistochemistry.Results HF model rats exhibited reduced food intake and urine output,dull and coarse fur,and decreased activity.HE and Masson staining revealed disorganized and disrupted myocardial fibers.These pathological features were ameliorated to varying degrees following intervention.Compared with the sham group,HF rats showed significantly reduced left ventricular ejection fraction(LVEF)and fractional shortening(LVFS),alongside elevated serum ANP and BNP levels and increased myocardial expression of Siat7A and GRP78 mRNA and protein(P＜0.05).All intervention groups demonstrated significant improvements in these parameters relative to the model group(P＜0.05).The SQJXF high-dose and sacubitril/valsartan groups exhibited more pronounced effects than the SQJXF low-dose group(P＜0.05).Conclusions SQJXF significantly improves ventricular structure and cardiac function in HF rats,reduces circulating biomarkers of heart failure,and attenuates myocardial fibrosis.These effects are likely mediated through regulation of Siat7A and GRP78 expression and subsequent suppression of ER stress.