An Experimental Study on the Improvement of Acute Myocardial Injury in Mice by Qishen Huanwu Capsules Through Inhibiting Necroptosis of Cardiomyocytes
Objective:To investigate the effect of Qishen Huanwu Capsules on acute myocardial injury caused by pirarubicin in mice and its underlying mechanism.Methods:30 male 12-week-old C57BU6 mice were ran-domly divided into control group,model group,low-dose group,medium-dose group,and high-dose group.Acute myocardial injury was induced by pirarubicin.Before tissue collection,body weight was measured,and left ventricu-lar structure and function were assessed using echocardiography.Serum levels of cardiac troponin Ⅰ(cTnI)and N-terminal pro-brain natriuretic peptide(NT-proBNP)were detected by ELISA.Histological changes in the myocar-dium were evaluated by HE staining.RT-qPCR was used to detect mRNA levels of pyroptosis-related genes[NOD-like receptor protein 3(NLRP3),gasdermin D(GSDMD),caspase-1(Caspase 1)]and necroptosis-related genes[interleukin-1α(IL-1α),IL-33,tumor necrosis factor-α(TNF-α),high mobility group box 1(HMGB1)]in myocardial tissue.Western blotting analysis was performed to detect protein levels of pyroptosis-related proteins(NLRP3,GSDMD,Cleaved-Caspase-1)and necroptosis-related proteins[phosphorylated mixed lineage kinase do-main-like protein(MLKL),phosphorylated receptor-interacting serine/threonine-protein kinase 3(RIP3),HMGB1].Results:Compared with the control group,the model group showed decreased activity,reduced body weight(P＜0.05),decreased ejection fraction(LVEF)(P＜0.05),increased serum cTnI and NT-proBNP levels(P＜0.05),and elevated myocardial injury scores(P＜0.05);levels of necroptosis-related genes and proteins were also increased(P＜0.05).Compared with the model group,Qishen Huanwu Capsules improved the general condition of the mice,increased body weight(P＜0.05),increased LVEF(P＜0.05),reduced serum cTnI and NT-proBNP lev-els,and ameliorated myocardial injury(P＜0.05).The expression of necroptosis-related genes and proteins was al-so decreased(P＜0.05).There were no significant differences in the expression of pyroptosis-related genes and proteins among the 5 groups(P＞0.05).Conclusion:Qishen Huanwu Capsules can improve acute myocardial inju-ry caused by pirarubicin,and this effect may be related to the inhibition of necroptosis in cardiomyocytes.
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