oxLDL通过TLR4诱导脂质累积和炎症反应促进动脉粥样硬化的分子机制

发布时间：2018-06-19 15:14

本文选题：TLR + 巨噬细胞　；参考：《上海交通大学学报(医学版)》2017年05期

【摘要】：目的·探究TLR4诱导脂质累积和炎症反应从而调控动脉粥样硬化的分子机制。方法·采用TLR4特异性siRNA敲除巨噬细胞,通过油红O染色法比较对照组和实验组中细胞内脂质含量;通过Western blotting检测CD36和血凝素样氧化低密度脂蛋白受体1(LOX-1)表达;通过ELISA检测白介素-6(IL-6)、IL-8、单核细胞趋化蛋白-1(MCP-1)和基质金属蛋白酶-9(MMP-9)等炎症因子的表达。结果·动脉粥样硬化斑块中巨噬细胞(CD68~+)大量聚集,且TLR4表达明显上调。ox LDL刺激巨噬细胞,可促进细胞中脂质累积(P0.01)并导致ox LDL相关受体CD36和LOX-1的表达上调以及炎症因子表达(P0.01)。特异性si RNA敲除TLR4可抑制ox LDL诱导的巨噬细胞内脂质累积(P0.01)和炎症因子分泌(P0.01),并影响ox LDL诱导的CD36表达,但对LOX-1表达没有影响。结论·ox LDL/TLR4可能通过上调CD36介导巨噬细胞中脂质累积和炎症反应,从而促进动脉粥样硬化发生和发展。
[Abstract]:Objective to investigate the molecular mechanism of TLR 4 inducing lipid accumulation and inflammatory response to regulate atherosclerosis. Methods TLR4 specific siRNA knockout macrophages were used to compare the intracellular lipid content between the control group and the experimental group by oil red O staining, and the expression of CD36 and hemagglutinin like oxidized low density lipoprotein receptor (1LOX-1) was detected by Western blotting. The expression of IL-8, monocyte chemotactic protein (MCP-1) and matrix metalloproteinase-9 (MMP-9) were detected by Elisa. Results in atherosclerotic plaques, macrophages (CD68 ~) were accumulated in large quantities, and TLR4 expression was upregulated. OxLDL stimulated macrophages (P0.01) and increased the expression of CD36 and LOX-1, as well as the expression of inflammatory cytokines (P0.01a) in Atherosclerotic plaques. Specific si RNA knockout (TLR4) inhibited the accumulation of lipid in macrophages induced by ox LDL (P 0.01) and the secretion of inflammatory factors (P 0.01), and affected the expression of CD36 induced by ox LDL, but had no effect on the expression of LOX-1. Conclusion ox LDL / TLR4 may promote the occurrence and development of atherosclerosis by up-regulating CD36 mediated lipid accumulation and inflammation in macrophages.
【作者单位】：上海交通大学医学院附属第九人民医院心内科;上海交通大学医学院附属瑞金医院心内科;
【分类号】：R543.5

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