强心汤调控IκBα/NF-κB p65信号通路介导的巨噬细胞M1极化治疗慢性心力衰竭的作用机制OA

OBJECTIVE To explore the mechanism of Qiangxin decoction in the treatment of chronic heart failure(CHF)by regulating the inhibitor of nuclear factor-κB alpha/nuclear factor-κB p65 subunit(IκBα/NF-κB p65)signaling pathway-mediated M1 macrophage polarization.METHODS In animal experiments,mice were used as research subjects,and the CHF model was established via coronary artery ligation.Model mice were treated with Qiangxin decoction(21.69 g/kg)for 28 days.After intervention,pathological morphological changes of myocardial tissues and cardiomyocyte apoptosis were observed.Serum levels of inflammatory factors including tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6),myocardial injury marker troponin I3(TNNI3),and macrophage-related markers F4/80 and cluster of differentiation 80(CD80)were detected.In cell experiments,monocyte-macrophage leukemia RAW264.7 cells were induced to undergo M1 polarization by 10 ng/mL lipopolysaccharide combined with 10 ng/mL interferon-γ,followed by 48 h intervention with 10%drug-containing serum of Qiangxin decoction.After intervention,the nuclear translocation of NF-κB p65 and NF-κB p50 was observed.The positive rate of CD80 in cells was measured.The mRNA expression of inflammatory factors including IL-1β,IL-6,IL-8,IL-18,TNF-α,inducible nitric oxide synthase(iNOS),cyclooxygenase-2(COX2),C-C motif chemokine receptor 7 isoform 2(CCR7-2),as well as the expression levels of proteins related to the IκBα/NF-κB p65 signaling pathway were detected.RESULTS Animal experimental results showed that Qiangxin decoction alleviated myocardial fibrosis in mice,and significantly reduced the cardiomyocyte apoptosis rate,serum levels of TNF-α and IL-6,as well as the protein expression of TNNI3,F4/80 and CD80 in myocardial tissues(P＜0.05).Cell experimental results indicated that Qiangxin decoction significantly suppressed the nuclear translocation of NF-κB p65 and NF-κB p50(P＜0.05).It significantly decreased the CD80 positive rate,mRNA levels of IL-1β,IL-6,IL-8,IL-18,TNF-α,iNOS,COX2 and CCR7-2,total and nuclear expression of NF-κB p65,total,nuclear and cytoplasmic expression of phosphorylated NF-κB p65,total expression of phosphorylated IκBα(P＜0.05).Meanwhile,it significantly elevated the total expression of IκBα and cytoplasmic expression of NF-κB p65(P＜0.05).CONCLUSIONS Qiangxin decoction can inhibit the activity of the IκBα/NF-κB p65 signaling pathway,reduce the release of pro-inflammatory factors,thereby restraining M1 macrophage polarization,mitigating myocardial fibrosis,and ultimately exerting therapeutic effects against CHF.