TLR4/NF-κB信号通路介导的血管炎症参与A型主动脉夹层的发病机制  

TLR4/NF-κB signaling pathway regulates inflammatory response involved in pathophysiological mechanisms of type A aortic dissection

作　　者：林镇业 王志文[1] 孟维鑫[1] 迟超[1] 展旭 刘宏宇[1] LIN Zhenye;WANG Zhiwen;MENG Weixin;CHI Chao;ZHAN Xu;LIU Hongyu(Department of Cardiac Vascular Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, P.R.China)

机构地区：[1]哈尔滨医科大学附属第一医院心脏大血管外科

出　　处：《中国胸心血管外科临床杂志》2019年第8期748-753,共6页Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

基　　金：国家临床重点专科建设项目

摘　　要：目的探讨Toll样受体-4(toll-like receptors-4,TLR4)信号通路的活化在A型主动脉夹层(type A aortic dissection,TAAD)发病中的作用及其机制。方法收集TAAD患者(n=12)和器官移植供体(n=12)的全层升主动脉壁组织样本;利用Western blotting检测TLR4信号通路相关蛋白表达,酶联免疫吸附法(ELISA)检测TAAD患者(n=43)和正常人体(n=50)的血液样品中白介素-1β(interleukin-1β,IL-1β)的表达。结果在TAAD患者的升主动脉壁内观察到TLR4信号通路及其主要分子的蛋白表达显著升高且伴有活化的巨噬细胞明显增多。TAAD患者血浆中IL-1β表达水平上升(P<0.05),多因素逻辑回归分析和受试者工作特征(ROC)曲线分析显示血浆中升高的IL-1β是TAAD的新型独立血浆标志物。结论活化的TLR4/NF-κB信号通路介导免疫炎症参与TAAD病理发病机制且其调控的炎症产物对TAAD患者具有重要的预测价值。Objective To investigate activated toll-like receptor-4(TLR4) signaling pathway involved in pathophysiological mechanisms of type A aortic dissection(TAAD). Methods Specimens of full-thickness ascending aorta wall from the TAAD patients(n=12) and the controlled donors(n=12) were collected. Western blotting was used to examine the associated proteins' expression of TLR4 signaling pathway. Blood samples from TAAD(n=43) and controlled patients(n=50) were examined by enzyme-linked immunosorbent assay(ELISA) to detect the circulating plasma cytokines levels of interleukin-1β(L-1β). Results In the aortic wall of TAAD, expression levels of TLR4 and protein expression of major molecule significantly elevated, and activated macrophages increased. Furthermore, elevated IL-1βlevels were observed in the TAAD patients' plasma compared with the control plasma. Multiple logistic regression analysis and receiver operating characteristic(ROC) curve showed that elevated IL-1β could be a novel and promising biomarker with important diagnostic and predictive value in the identification of TAAD. Conclusion Activated TLR4/NF-κB signaling pathway regulates inflammatory response to involve in pathophysiological mechanisms of type A aortic dissection and its regulated inflammatory products have important predictive value for patients with TAAD.

关 键 词：A型主动脉夹层 免疫炎症 TOLL样受体-4 生物标记物 

分 类 号：R543.1[医药卫生—心血管疾病]