1.Effect of neferine on myocarditis in heart failure rats by regulating CCL2-CCR2 signaling axis
Wenjing WANG ; Yanhui NI ; Yuxuan LI ; Feifei ZHANG ; Yuetao XIE ; Litian LIU
Chinese Journal of Immunology 2024;40(12):2543-2547,2553
Objective:To investigate effect of neferine(NeF)on myocarditis in heart failure(HF)rats by regulating CC-che-mokine ligand 2/CC chemokine receptor 2(CCL2-CCR2)signaling axis.Methods:HF rat model was constructed by ligating left ante-rior descending branch,and randomly separated into HF group,different doses of NeF groups(5 mg/kg,10 mg/kg,20 mg/kg),20 mg/kg NeF+CCL2 group,another 10 rats without ligating left anterior descending branch were regarded as sham surgery group.After treatment,cardiac function[left ventricular end systolic diameter(LVESD),ejection fraction(EF),left ventricular ejection fraction(LVEF)]were evaluated.Serum indicators[brain natriuretic peptide(BNP),IL-1β,N-terminal B-type natriuretic peptide(NT-pro BNP),TNF-α]were detected.Myocardial tissue was isolated and expressions of TNF-α and IL-1β,pathological damage,collagen deposition,expressions of CCL2 and CCR2 proteins were detected.Results:Compared with sham surgery group,HF group showed a decrease in myocardial cells,infiltration of inflammatory cells,and severe deposition of collagen fibers,LVESD,serum BNP,NT-pro BNP,TNF-α,IL-1β levels,myocardial tissue TNF-α,IL-1β expressions,collagen area ratio,CCL2,CCR2 protein expressions were greatly increased,LVEF and EF were greatly decreased(P<0.05).Compared with HF group,central muscle tissue damage and collagen fiber deposition were reduced in different doses of NeF groups,LVESD,serum BNP,NT-pro BNP,TNF-α,IL-1β levels,myocardial tissue TNF-α,IL-1β expressions,collagen area ratio,CCL2,CCR2 protein expressions were greatly decreased,LVEF and EF were greatly increased,with differences between groups(P<0.05).After CCL2 intervention,compared with 20 mg/kg NeF group,myocardial tissue damage and collagen fiber deposition were worsened,LVESD,serum BNP,NT-pro BNP,TNF-α,IL-1β levels,myocardial tissue TNF-α,IL-1β expressions,collagen area ratio,CCL2,CCR2 protein expressions were greatly increased,LVEF and EF were greatly decreased(P<0.05).Conclusion:NeF regulates CCL2-CCR2 signaling axis,inhibits myocar-ditis in HF rats,and improves cardiac function.