A20/NLRP3炎症小体信号通路在急性冠脉综合征PCI患者冠脉无复流中的作用

Role of A20/NLRP3 inflammasome signaling pathway in coronary no-reflow of patients with acute coronary syndrome undergoing PCI

目的探索A20/NLRP3炎症小体信号通路与急性冠脉综合征(ACS)患者经皮冠状动脉介入治疗(PCI)过程中发生冠脉无复流的相关性,明确A20/NLRP3炎症小体信号通路在冠脉无复流中的可能作用。方法连续收集行PCI手术而发生冠脉无复流的100例ACS患者为研究对象,并选择同时期冠脉血流正常的ACS患者200例为对照。根据冠状动脉造影心肌梗死溶栓(TIMI)血流分级定义冠脉复流情况。分离纯化外周血单个核细胞(PBMC),并利用Western blot和实时定量PCR对PBMC中A20和NLRP3的蛋白和mRNA表达水平进行检测。利用ELISA法检测血浆IL-1β。最后将全球急性冠脉综合征注册(GRACE)积分与血浆IL-1β水平进行相关性分析。结果基线资料显示,冠脉无复流组患者较正常血流组患者年龄增高(66.52±10.85岁vs 60.50±11.25岁,P<0.001)。而且,与正常血流组相比,无复流组患者吸烟及合并糖尿病人数占比均增多,差异有统计学意义(P<0.05)。与冠脉血流正常组相比,冠脉无复流组患者PBMC中A20蛋白表达水平降低(P<0.05),而NLRP3蛋白水平升高(P<0.01)。冠脉无复流组患者较血流正常组患者PBMC中A20的mRNA表达水平降低(P<0.001),而NLRP3的mRNA表达水平升高(P<0.05)。与冠脉血流正常组相比,无复流组患者血浆IL-1β水平升高[(3.78±0.33)pg/ml vs(5.11±0.65)pg/ml,P<0.05]。所有研究对象的血浆IL-1β水平与GRACE评分呈显著正相关(r=0.4151,P<0.001)。结论A20/NLRP3炎症小体信号通路与ACS患者PCI无复流密切相关,A20/NLRP3炎症小体信号通路可能成为ACS患者PCI无复流的有效干预靶点。

Objective To explore the relationship between tumor necrosis factorα-induced protein 3(A20)/nucleotide-binding oligomerization domain,leucine-rich repeat and pyrin domain-containing 3(NLRP3)inflammasome signaling pathway and coronary artery no-reflow in patients with acute coronary syndrome(ACS)during percutaneous coronary intervention(PCI),and to clarify the possible role of A20/NLRP3 inflammasome signaling pathway in coronary artery no-reflow.Methods A total of 100 ACS patients undergoing PCI with coronary artery no-reflow were selected as the study objects,and 200 ACS patients with normal coronary blood flow during the same period were selected as the controls.Coronary no reflow was identified according to the thrombolysis in myocardial infarction(TIMI)flow of coronary angiography.Peripheral blood mononuclear cells(PBMCs)were isolated and purified,and the protein and mRNA expression levels of A20 and NLRP3 in PBMCs were detected by Western blot and real-time quantitative PCR,respectively.Plasma IL-1βwas detected by ELISA.Finally,the correlation between the global registry of acute coronary events(GRACE)score and plasma IL-1βlevel was analyzed.Results Baseline data showed that the patients with coronary no reflow were older than those with normal flow(66.52±10.85 years old vs 60.50±11.25 years old,P<0.001).In addition,the percentages of smokers and diabetic patients in no reflow group were more than those in normal group.Compared with normal flow group,the A20 protein expression in PBMC was decreased in no reflow group(P<0.05),but the expression of NLRP3 protein was increased(P<0.01).The A20 mRNA expression level in PBMC of patients with no reflow was lower than that of patients with normal blood flow(P<0.001),but the mRNA expression level of NLRP3 was higher(P<0.05).Compared with normal flow group,plasma IL-1βlevel was increased in patients with no reflow[(3.78±0.33)pg/ml vs(5.11±0.65)pg/ml,P<0.05].Moreover,plasma IL-1βlevel was significantly positively correlated with the GRACE score in all subjects(r=0.4151,P<0.001).Conclusion A20/NLRP3 inflammasome signaling pathway is closely related with coronary no reflow during PCI in patients with ACS,and may become an effective intervention target for PCI-related no reflow in patients with ACS.