TLR4在冠状动脉粥样硬化性心脏病患者单个核细胞炎性反应中的作用

The role of TLR4 on mononuclear cell mediated inflammatory reaction in patients with coronary arteriosclerosis disease

目的探讨冠状动脉粥样硬化性心脏病患者外周血单个核细胞Toll样受体4（Toll—like receptor4，TLR4）介导的炎性反应及在急性冠状动脉事件中的作用。方法连续人选研究对象，取外周血分离单个核细胞，予以脂多糖（LPS）和（或）阿托伐他汀处理。流式细胞仪检测细胞TLR4表达，ELISA法检测肿瘤坏死因子（TNF）-α、白细胞介素（IL）-6、IL-1、IL-10水平。结果急性冠状动脉综合征（ACS）组单个核细胞TLR4及TNF-α、1L-6、IL-1明显高于稳定型心绞痛（SAP）组、冠状动脉慢血流（CSF）组及健康对照（HC）组，而IL-10低于其他各组（P〈0．05）。LPS刺激后，与HC组比较，SAP组、CSF组TLR4及TNF—α、IL-6、IL-1明显高于原有水平，IL-10低于原有水平（P〈0．05），而阿托伐他汀干预能抑制这一现象。阿托伐他汀干预ACS组可致TLR4和TNF—α、IL-6、IL-1水平下降，IL-10水平上升（P〈0．05）。结论TLR4过度表达及其炎症反应可能与ACS的发生密切相关。LPS能激活SAP患者、CSF患者单个核细胞TLR4，介导炎性反应。阿托伐他汀能抑制TLR4的过度表达及其炎性反应。

Objective The study aims to explore toll-like receptor 4 （TLR4） on peripheral blood mononuclear cell mediated inflammatory reaction in patients with coronary arteriosclerosis disease and coronary slow flow. Methods Patients were selected and divided into acute coronary syndrome （ACS） group, stable angina pectoris （SAP） group, coronary slow flow （CSF） group and healthy control （HC） group. Twenty ml blood was collected to separate the mononuclear cells using Lymphocytes Separation Medium. The mononuclear ceils were intervened with lipopolysaccharide （LPS） and/or atorvastatin. The expression of TLR4 on peripheral blood mononuclear cell was analyzed by flow cytometry and the concentration of tumor necrosis factor （TNF）-α, interleukin （IL）-6, IL-1 and IL-10 in plasma or culture medium were measured by enzyme linked immunosorbent assay （ELISA）. Results Before intervention, the levels of TLR4, TNF-α, IL- 1 and IL-6 were significantly higher, but the level of IL- 10 was significantly lower from in the ACS group compared with the SAP, CSF and HC groups. The expressions of TLR4, TNF-α, IL-1 and IL-6 were significantly increased, but the levels of IL-10 was significantly decreased in the SAP and CSF groups after LPS stimulation, compared with HC group. These changes can be reversed by atorvastatin intervention. Conclusion The results suggest that over-expression of TLR4 and inflammatory cytokines could be closely related to ACS. LPS can induce TLR4 of peripheral blood mononuclear cell mediated inflammatory response in patients with stable angina and coronary slow flow. Atorvastatin can inhibit the over-expression of TLR4 and this inflammatory response.