Yixin Formula Inhibits NLRP3 Inflammasomes Mediated Pyroptosis to Attenuates Myocardial IschemiaReperfusion Injury in Rats
Objective To investigate the possible mechanism of myocardial protective effect of Yixin formula in rats with myocardial ischemia-reperfusion injury.Methods Sixty-five rats were randomly divided into 10 in the sham-operated group and 55 in the modeling group;the modeling group was constructed by ligating the left anterior descending branch of the coronary artery,and the sham-operated group was only threaded without ligation.The modeling group was randomly divided into model group,Yixin formula low,medium and high dose group and trimetazidine group after membrane creation.The low,medium and high dose groups of Yixin formula were given 6.84 g·kg-1,13.68 g·kg-1 and 27.36 g·kg-1 of Yixin formula and 5.4 mg·kg-1 of Trimetazidine respectively,and the sham-operated group and the model group were given equal volume of saline by gavage for 7 days in each group.Echocardiography was used to detect the cardiac function of rats;biochemical methods were used to detect serum creatine kinase(CK),lactate dehydrogenase(LDH)and glutamate transaminase(AST);hematoxylin-eosin(HE)staining was used to observe the histopathological changes of rat myocardium;Masson staining was used to observe the degree of myocardial fibrosis;TUNEL staining for myocardial cell apoptosis index;Western blot was performed to detect NLRP3,pro-Caspase-1 and GSDMD-FL、GSDMD-N protein expression in myocardial tissue.Results Compared with the sham-operated group,the model rats showed significantly lower left ventricular ejection fraction(LVEF)and LV short-axis shortening percentage(FS)(P＜0.001),significantly higher myocardial injury markers CK,AST,and LDH(P＜0.001),pathological findings showed myocardial structural damage,interstitial edema with inflammatory cell infiltration,disorganized myocardial fiber arrangement,larger myocardial cell cross-sectional The pathological results showed that myocardial structure was damaged,interstitial edema with inflammatory cell infiltration,disorganized myocardial fiber arrangement,large cross-sectional area of myocardial cells(P＜0.001),significant myocardial collagen fibrosis(P＜0.001),the pyroptosis index of myocardial cells was increased(P＜0.001),and significantly increased NLRP3,pro-Caspase-1,GSDMD-FL,and GSDMD-N protein expression in myocardial tissues(P＜0.001).Compared with the model group,LVE and FS were significantly higher in each dose group of Yixin formula and trimetazidine group(P＜0.05,P＜0.001),myocardial injury markers CK,AST and LDH were significantly decreased(P＜0.05,P＜0.01,P＜0.001),myocardial cell cross-sectional area was reduced(P＜0.05,P＜0.001),myocardial fibrosis was reduced to different degrees(P＜0.001),the apoptosis index of cardiomyocytes was decreased(P＜0.05,P＜0.001),and NLRP3,pro-Caspase-1,and GSDMD protein expression in myocardial tissue was reduced(P＜0.001).Conclusion Yixin formula can reduce myocardial injury and the degree of myocardial fibrosis,and thus improve the cardiac function in rats.and its mechanism may be related to down regulating NLRP3/Caspase-1/GSDMD signaling pathway and inhibiting cardiomyocyte pyroptosis.
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