Alleviation of myocardial injury with Shenfu Injection through regulating Nrf2/HO-1 signaling pathway in spontaneous hypertensive rats
Hu Fangxin
Kong Fanying
Zhang Qiang
Feng Liang
Li Xinfeng
Abstract：Objective To study the influence of Shenfu Injection(SFI)on myocardial injury in spontaneous hypertensive rats(SHR),and discuss the effect of signaling pathway of nuclear factor E2 related factor 2/heme oxygenase 1(Nrf2/HO-1).Methods SHR(n=40)were randomly divided into model group(given intraperitoneal injection of normal saline,once/d),captopril group(given intraperitoneal injection of captopril,7 mg/kg,once/d),and low-dose,mid-dose and high-dose SFI groups(given intraperitoneal injection of SFI,respectively in dose of 1 ml/kg,2 ml/kg,4 ml/kg,once/d,each n=5).And other 8 WKY rats were chosen into normal control group(given intraperitoneal injection of normal saline,once/d).After4-week treatment,the levels of systolic blood pressure(SBP),diastolic blood pressure(DBP)and mean arterial pressure(MAP)were detected in all groups.The indexes of heart function[left ventricular end-systolic diameter(LVESD),left ventricular end-diastolic diameter(LVEDD),ejection fraction(EF),fraction shortening(FS)]were detected by using ultrasonic inspection.The indexes of serum myocardial enzyme[aspartate aminotransferase(AST),creatine kinase-MB isoenzyme(CK-MB)and cardiac troponin I(cTnI)]were detected by using ELISA.The indexes of serum oxidative stress[malondialdehyde(MDA),superoxide dismutase(SOD),catalase(CAT)]were detected by using spectrophotometry.The myocardial histopathological changes and cardiomyocyte apoptosis were detected by using HE or TUNEL staining.The ultrastructural changes of myocardial cells were observed by using transmission electron microscope(TEM).The expression of Nrf2/HO-1 signaling pathway related proteins were detected by using Western blotting assay.Results Compared with normal control group,SBP,DBP,MAP,LVESD,LVEDD,AST,CK-MB,cTnI,MDA increased significantly,and EF,FS,SOD and CAT decreased significantly in model group(P＜0.05).The myocardial histopathological changes were observed in myocardial fibers and cardiomyocytes,cardiomyocyte apoptosis was higher and apoptosis index(AI)increased significantly in model group.The protein expressions of Nrf2,HO-1 and Bcl-2 decreased significantly,expressions of Bax and cleaved caspase-3 and ratio of Bax/Bcl-2 and cleaved caspase-3/caspase-3increased significantly in model group compared with normal control group(P＜0.05).Compared with model group,SBP,DBP,MAP,LVESD,LVEDD,AST,CK-MB,cTnI,MDAdecreased significantly(P＜0.05),and EF,FS,SOD and CAT increased significantly(P＜0.05)in captopril groupand mid-dose and high-dose SFI groups.Compared with model group,myocardial histopathological changes and cardiomyocyte apoptosis were relieved in varying degrees and AI decreased significantly(P＜0.05),and cardiomyocyteultrastructural changes were relieved in captopril groupand low-dose,mid-dose and high-dose SFI groups.Compared with model group,the protein expressions of Nrf2,HO-1 and Bcl-2 increased significantly,and expressions of Bax and cleaved caspase-3 and ratio of Bax/Bcl-2,and cleaved caspase-3/caspase-3 decreased significantly in captopril groupand mid-dose and high-dose SFI groups(P＜0.05).The above effects of SFI showed a certain dose dependence.Conclusion SFI has the effects of relieving myocardial injury and improving heart function in SHR,which may be related to activation of Nrf2/HO-1 signaling pathway and inhibitions of oxidative stress and apoptosis.
Keywords：Spontaneous hypertensionShenfu InjectionMyocardial injuryOxidative stressApoptosisNuclear factor E2 related factor 2/heme oxygenase 1 signaling pathwayRats
Publication Date：2025-01-27
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：7( 52-58 )