中国胸心血管外科临床杂志

中国胸心血管外科临床杂志

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

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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 discuss 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 TAAD patients (n=12) and 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) and control patients. 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-1β levels were observed in TAAD patients’ plasma compared with control plasma. Multiple logistic regression analysis and receiver operating characteristic curve (ROC) showed that elevated IL-1β could be a novel and promising biomarker with important diagnostic and predictive value in the identification of TAAD. Conclusion Actived 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; TLR4; 生物标记物

Key words: Stanford type A aortic dissection; immunity-inflammation; TLR4; biomarker

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