甲基莲心碱调节CCL2-CCR2信号轴对心力衰竭大鼠心肌炎症的影响  

Effect of neferine on myocarditis in heart failure rats by regulating CCL2-CCR2 signaling axis

作　　者：王文静[1] 倪艳辉[1] 李玉璇 张飞飞[1] 谢悦陶[1] 刘立天 WANG Wenjing;NI Yanhui;LI Yuxuan;ZHANG Feifei;XIE Yuetao;LIU Litian(The Fourth Department of Cardiovascular Medicine,Hebei Provincial People's Hospital,Shijiazhuang 050051,China)

机构地区：[1]河北省人民医院心血管内四科,石家庄050051

出　　处：《中国免疫学杂志》2024年第12期2543-2547,2553,共6页Chinese Journal of Immunology

摘　　要：目的:探讨甲基莲心碱(NeF)调节趋化因子CCL2/受体CCR2(CCL2-CCR2)信号轴对心力衰竭(HF)大鼠心肌炎症的影响。方法:通过结扎左前降支构建HF大鼠模型,随机分为HF组、不同剂量(5、10、20 mg/kg)NeF组以及20 mg/kg NeF^(+)CCL2组,并选取不结扎左前降支的10只大鼠作为假手术组,治疗结束后进行心脏功能[左室收缩末期内径(LVESD)、射血分数(EF)、左心室射血分数(LVEF)]评估;检测血清指标[脑钠肽(BNP)、IL-1β、N末端B型利钠肽原(NT-pro BNP)、TNF-α];分离心肌组织,检测组织中TNF-α、IL-1β表达、病理损伤、胶原沉积以及CCL2、CCR2蛋白表达。结果:HF组大鼠心肌细胞减少,炎症细胞浸润,胶原纤维沉积严重,LVESD、血清中BNP、NT-pro BNP、TNF-α、IL-1β水平、心肌组织中TNF-α、IL-1β表达、胶原面积比、CCL2、CCR2蛋白表达较假手术组显著升高,LVEF、EF显著降低(P<0.05);不同剂量NeF组大鼠心肌组织损伤、胶原纤维沉积减轻,LVESD、血清中BNP、NT-pro BNP、TNF-α、IL-1β水平、心肌组织中TNF-α、IL-1β表达、胶原面积比、CCL2、CCR2蛋白表达较HF组显著降低,LVEF、EF显著升高,且组间差异具有统计学意义(P<0.05);CCL2干预后,心肌组织损伤、胶原纤维沉积加重,LVESD、血清中BNP、NT-pro BNP、TNF-α、IL-1β水平、心肌组织中TNF-α、IL-1β表达、胶原面积比、CCL2、CCR2蛋白表达较20 mg/kg NeF组显著升高,LVEF、EF显著降低(P<0.05)。结论:NeF调节CCL2-CCR2信号轴抑制HF大鼠心肌炎症,改善心功能。Objective:To investigate effect of neferine(NeF)on myocarditis in heart failure(HF)rats by regulating CC-chemokine ligand 2/CC chemokine receptor 2(CCL2-CCR2)signaling axis.Methods:HF rat model was constructed by ligating left anterior 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-αand 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-1βlevels,myocardial tissue TNF-α,IL-1βexpressions,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-1βlevels,myocardial tissue TNF-α,IL-1βexpressions,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-1βlevels,myocardial tissue TNF-α,IL-1βexpressions,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 myo

关 键 词：甲基莲心碱 CCL2-CCR2信号轴 心力衰竭 心肌炎症 

分 类 号：R285.5[医药卫生—中药学]