Protective Effects And Mechanism Of Shenfu Injection Based On Apelin/APJ System And Endoplasmic Reticulum Stress In Rats With Myocardial Ischemia-reperfusion Injury

Objective: Shenfu injection is widely used in the clinical treatment of acute heart failure due to ischemia-reperfusion injury.However,the molecular mechanism by which ginseng injection acts remains unclear.Studies have shown that activation of both the apelin/APJ system and endoplasmic reticulum stress occurs in I/R.The aim of this study was to verify:the relationship between apelin/APJ expression and endoplasmic reticulum stress-induced apoptosis during myocardial ischemia-reperfusion treated with SFI.Methods: Fifty SD male rats were randomly divided into sham-operated group,myocardial ischemia-reperfusion model group(I/R group),and Shenfu injection low,medium and high dose groups(SFI-L,SFI-M,SFI-H)according to the random number table method,10 rats in each group.Echocardiography was performed to detect left ventricular ejection fraction(LVEF)and left ventricular short-axis shortening(LVFS)in rats with ischemia-reperfusion injury;enzyme-linked immunosorbent assay was performed to detect creatine kinase isoenzyme(CK-MB),lactate dehydrogenase(LDH),interleukin IL-1β(IL-1β),interleukin IL-6(IL-6),interleukin IL-18(IL-18)18)and TNF-α tumor necrosis factor-α(TNF-α)levels;HE staining to detect cardiomyocyte structure;immunohistochemistry to detect apelin,APJ and CHOP protein expression;protein blotting to detect apelin,APJ and CHOP protein expression levels.Rat cardiomyocytes H9c2 were divided into 6 groups: control group,hypoxia/reoxygenation group,Shenfu injection low,medium and high dose group(SFI-L,SFI-M,SFI-H)and ML221 group.Cell viability of each group was detected by tetramethylazole salt(MTT)method,apoptosis level of H9c2 cardiomyocytes was detected by flow cytometry,and apelin,APJ and CHOP protein expression levels were detected by protein blotting.Results: Echocardiography showed that SFI significantly improved left ventricular ejection fraction(LVEF)and left ventricular short-axis shortening(LVFS)in rats with ischemia-reperfusion injury;serum Elisa assay showed that SFI downregulated the expression levels of serum inflammatory factors IL-6,IL-1β,TNF-α and IL-18 in rats with ischemia-reperfusion injury;HE staining showed that SFI reduced myocardial cell HE staining showed that SFI reduced structural damage to myocardial cells,and immunohistochemistry and Western blot showed that SFI promoted apelin and APJ expression in vivo and in vitro,and inhibited the expression of CHOP,an apoptosis-related protein induced by ER stress.Conclusion: The apelin/APJ system is an important mechanism of SFI in the treatment of myocardial ischemia/reperfusion injury.SFI protects against myocardial ischemia/reperfusion by increasing the expression levels of apelin and APJ,thereby inhibiting endoplasmic reticulum stress-induced apoptosis.