Inhibitory Effect of Sarkubatril/Valsartan on Myocardial Fibrosis in Rats with Chronic Heart Failure by Regulating Nrf2/HO-1 Pathway
WANG Zhuoyi
HUANG Yiting
Abstract：Objective:To investigate the effect and mechanism of sacubactril/valsartan(SV)on myocardial fibrosis in rats with chronic heart failure(CHF).Methods:The fifty SD rats were randomly divided into Control group(10 rats)and modeling group(40 rats).The CHF rat model was constructed by subcutaneous injection of isoproterenol.The successful modeling rats were randomly divided into CHF group,SV group,and SV+Nrf2 inhibitor(ML385)group,with 10 rats in each group.The rats of SV group were gavaged with 68 mg/(kg·d)SV.The rats of SV+ML385 group were gavaged with 68 mg/(kg·d)SV combined with 30 mg/kg ML385 intraperitoneally.The rats in Control group and CHF group were gavaged with the same volume of normal saline.After 3 months,the cardiac function indexes were measured by ultrasound.The morphological and structural changes of myocardium were detected by histopathological staining.The protein expressions of Collagen Ⅰ and Collagen Ⅲ in myocardial tissue were detected by immunohistochemistry.The levels of superoxide dismutase(SOD)and malondialdehyde(MDA)in myocardial tissue were determined by biochemical detection.The expressions of Nrf2 and HO-1 protein in cardiac tissue were detected by Western Blot.Results:Compared with the Control group,the cardiac function indexes in the CHF group significantly changed,the myocardial structure showed typical pathological injury and Collagen deposition increased,the protein expression of Collagen Ⅰ and Ⅲ in myocardial tissue was positive,and the level of MDA increased(P＜0.05),while the protein expressions of SOD level,Nrf2 and HO-1 decreased(P＜0.05).Compared with the CHF group,the above indexes of SV group significantly inhibited and myocardial fibrosis improved in rats with CHF(P＜0.05).Compared with the SV group,ML385 reversed the protective effect of SV on myocardial fibrosis in CHF rats.Conclusion:SV could improve myocardial fibrosis in CHF rats,and its mechanism was related to activating Nrf2/HO-1 pathway and inhibiting of myocardial oxidative stress.
Keywords：chronic heart failuresacubatrol/valsartanfibrosisnuclear factor E2 related factor 2/heme oxygenase-1oxidative stressratsexperimental study
Publication Date：2025-05-25
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：6( 1488-1493 )