Inhibition of the NLRP3 inflammasome limits the inflammatory injury following myocardial ischemia-reperfusion in the mouse
Inhibition of the NLRP3 inflammasome limits the inflammatory injury following myocardial ischemia-reperfusion in the mouse
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DOI：
10.1016/j.ijcard.2016.02.043
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发表时间：
2016-04-15
影响因子：
3.5
通讯作者：
Abbate, Antonio
中科院分区：
文献类型：
--
作者：
Toldo, Stefano;Marchetti, Carlo;Abbate, Antonio
背景：成功的再通是减少急性心肌梗死(AMI)缺血损伤的最有效策略。然而，缺血损伤也会触发一种称为再灌流损伤的继发性非缺血非依赖性损伤，从而导致整体的梗塞面积。我们假设抑制NOD样受体蛋白-3(NLRP3)炎性小体通过抑制再灌注损伤的炎性成分来限制心肌缺血/再灌注(I/R)后的梗塞范围。方法：CD-1雄性小鼠短暂结扎冠状动脉左前降支300175min后再灌流。结果：心肌梗死面积在再灌注后1、3、24 h呈时间依赖性增加(分别为危险面积的11.2%、305%和43.4%；P<；0.001为趋势)。NLRP3在24 h和6 h较3h表达显著增加(P
Background: Successful reperfusion is the most effective strategy to reduce ischemic injury in acute myocardial infarction (AMI). lschemic injury, however, also triggers a secondary ischemia-independent injury, known as re perfusion injury, contributing to the overall infarct size. We hypothesize that inhibition of the Nod-like Receptor Protein-3 (NLRP3) inflammasome limits infarct size following myocardial ischemia/reperfusion (I/R), by inhibiting the inflammatory component of the reperfusion injury.Methods: CD-1 male mice underwent transient ligation of the left anterior descending coronary artery for 3001 75 min followed by reperfusion. Infarct size was measured at 1, 3 and 24 h. A NLRP3 inflammasome inhibitor (NLRP3inh) or vehicle was administrated immediately at time of reperfusion or with a delay of 1 or 3 h of reperfusion.Results: A time -dependent increase in infarct size was measured at 1,3, and 24 h after reperfusion (11 2%, 305% and 43 4% of the area at risk respectively; P < 0.001 for trend). NLRP3 myocardial expression was significandy increased at 24 h and 6 h vs 3 h (P