大鼠急性心肌梗死后NLRP3炎性体-IL-1β信号轴激活与End-MT的关系

Relationship between NLRP3 inflammasome-IL-1β axis and End-MT after acute myocardial infarction in rats

目的:研究在急性心肌梗死(acute myocardial infarction,AMI)引发的心肌纤维化过程中,NLRP3炎性体-IL-1β信号轴的激活与内皮-间充质转化(endothelial-mesenchymal transition,End-MT)是否存在同一性。方法:30只成年雄性SD大鼠随机分为假手术组(n=15)与AMI组(n=15),术后28 d采用Masson染色检测心肌纤维化水平;Western blot检测NLRP3炎性体(NLRP3、ASC、pro-caspase-1和caspase-1)、内皮细胞标志物(CD31和VE-cadherin)及间充质细胞标志物(α-SMA和FSP1)的表达;酶联免疫吸附法检测NLRP3炎性体下游因子IL-1β的表达。结果:与假手术组相比,冠脉结扎组AMI大鼠心肌纤维化水平、End-MT进展程度、NLRP3炎性体活性及caspase-1和IL-1β的表达均显著增加(P<0.05)。结论:NLRP3炎性体-IL-1β信号轴的激活与End-MT进程具有显著同一性,提示NLRP3炎性体-IL-1β作为激活End-MT的潜在靶点将为研究AMI后心肌纤维化及心力衰竭提供新的理论依据。

AIM:To investigate whether activation of NLRP3 inflammasome-IL-1βaxis is consistent with endothelial-mesenchymal transition(End-MT)during the process of myocardial fibrosis after acute myocardial infarction(AMI).METHODS:Adult male SD rats(n=30)were randomly divided into sham operation group(n=15)and AMI group(n=15).After 28 d,Masson staining was used to detect the level of myocardial fibrosis.The activation of NLRP3 inflammasome including NLRP3,ASC,pro-caspase-1 and caspase-1,the endothelial cell markers CD31 and VE-cadherin,and the mesenchymal cell markersα-SMA and FSP1 were analyzed by Western blot.The expression of IL-1βwas measured by ELISA.RESULTS:The levels of myocardial fibrosis and End-MT,the activation of NLRP3 inflammasome,and the expression of caspase-1 and IL-1βwere significantly increased in AMI group compared with sham operation group(P<0.05).CONCLUSION:The activation of NLRP3 inflammasome-IL-1βaxis is significantly consistent with End-MT process,suggesting that NLRP3 inflammasome-IL-1β,as a potential target for the activation of End-MT,will provide a novel theoretical target for the treatment of myocardial fibrosis and heart failure after AMI.