Objective To explore the molecular mechanism of Sacubitril/Valsartan Sodium improving heart failure cell model and animal model through Nrf2/HO-1 signaling pathway.Methods H9C2 cells were treated with Doxorubicin hydrochloride(DOX)to construct a heart failure cell model,and then treated with Sacubitril/Valsartan Sodium(LCZ696)and Nrf2 inhibitor(ML385),respectively.They were divided into five groups:Control,DOX,DOX+LCZ696,DOX+ML385,DOX+LCZ696+ML385.Mice model of heart failure was induced by DOX and treated with LCZ696 and ML385,which were divided into sham operation group,DOX group,DOX+LCZ696 group,and DOX+LCZ696+ML385 group.Cell viability and apoptosis was analyzed by CCK-8 and flow cytometry.ROS,MDA and SOD levels were detected with the kit.The levels of TNF-α,IL-1β and IL-6 were detected by ELISA.Bax,Bcl-2,C-caspase-3,Nrf2 and HO-1 proteins was detected via Western blotting.Heart tissue of mice with heart failure was stained by HE,Masson and TUNEL.Results Compared with control group,DOX-induced cell viability was significantly decreased(P＜0.05);cell apoptosis ratio was increased(P＜0.05);the levels of inflammatory factors,ROS,MDA,and pro-apoptotic proteins were increased(P＜0.05);SOD level,Nrf2,and HO-1 proteins were decreased(P＜0.05).Compared with DOX group,DOX+LCZ696 group significantly inhibited cell damage caused by DOX,while DOX+ML385 group significantly aggravated cell damage.Compared with DOX+LCZ696 group,the cell injury was more severe in DOX+LCZ696+ML385 group,while the cell injury was reduced in DOX+LCZ696+ML385 group.Compared with the sham group,the heart tissue damage of mice induced by DOX was serious,the damage caused by DOX was alleviated in DOX+LCZ696 group,and the damage was aggravated in DOX+LCZ696+ML385 group.Conclusion Sacubitril/Valsartan sodium alleviates DOX-induced myocardial cell injury through Nrf2/HO-1 signaling pathway.
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