Protective effect of Noxintuo on cardiac function in a heart failure model with preserved ejection fraction based on NLRP3-mediated cell pyroptosis
YANG Xiaodong
SHEN Shiyu
Abstract：Objective To investigate the protective effect of Sakubatrir valsartan(trade name:Noxintuo)on cardiac function in rats with heart failure with preserved ejection fraction(HFpEF)based on NOD-like receptor protein 3(NLRP3)-mediated cell apoptosis.Methods The rats were randomly divided into sham group,HFpEF group,and sacubitril/valsartan(Sac/Val)group.Cardiac ultrasound was used to assess cardiac function parameters.Enzyme-linked immunosorbent assay(ELISA)was performed to measure the serum levels of N-terminal prohormone of brain natriuretic peptide(NT-proBNP).The hematoxylin and eosin(H&E)staining was used to evaluate histopathological changes in cardiac tissue.TdT-mediated dUTP nick end labeling(TUNEL)assay was used to assess apoptosis.Western blot was performed to detect protein levels of Caspase-1,NLRP3,gasdermin D(GSDMD),interleukin-1 beta(IL-1β)and IL-18.Results The left ventricular ejection fraction(LVEF),left ventricular end-diastolic diameter(LVEDD),and early/late diastolic tricuspid inflow velocity ratio(E/A)of the HFpEF group were significantly lower than those of the sham group,while the interventricular septum thickness(IVSd),left ventricular posterior wall end diastole(LVPEd),left ventricular posterior wall end systole(LVPWs),and early tricuspid inflow velocity/early diastolic tricuspid annular velocity ratio(E/E')were significantly higher than those of the sham group(P＜0.05).Compared with those of the HFpEF group,the Sac/Val group showed significantly higher LVEF,LVEDD,and E/A,but significantly lower IVSd,LVPEd,LVPWs,and E/E'(P＜0.05).Compared with those of the sham group,heart weight/body mass index(Hw/W),left ventricular weight/body mass index(LVw/W)and NF proBNP were significantly higher in the HFpEF group(P＜0.05).Compared with those of the HFpEF group,the Sac/Val group showed significantly lower Hw/W,LVw/W,and NF proBNP levels(P＜0.05).Compared with that of the sham group,the apoptotic rate of myocardial cells in the HFpEF group was significantly higher(P＜0.05).Compared with that of the HFpEF group,the apoptotic rate of myocardial cells in the Sac/Val group was significantly lower(P＜0.05).The protein expressions of NLRP3,Caspase-1,GSDMD,IL-1 β,and IL-18 proteins in rat myocardial tissue of HFpEF group were significantly higher than those of sham group(P＜0.05),while the expressions of NLRP3,Caspase-1,GSDMD,IL-1 β,and IL-18 in the myocardial tissue of Sac/Val group rats were significantly lower than those of HFpEF group(P＜0.05).Conclusion Noxintuo can improve diastolic function and inhibit myocardial fibrosis in rats with HFpEF by inhibiting NLRP3-mediated myocardial cell pyroptosis.
Keywords：NOD-like receptor protein 3(NLRP3)-mediated cell apoptosisSakubatrir valsartanheart failure with preserved ejection fractioncardiac function
Publication Date：2025-08-26
Online Publishing Date：2025-09-12(First online date of this platform, not the publication date of the document)
Pages：5( 1283-1287 )