上海交通大学学报（医学版）

上海交通大学学报（医学版）

• 论著（基础研究） • 上一篇    下一篇

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

查晴 1，曹丽娟 1*，王燕萍 2，杨克 2，刘艳 1   

  1. 上海交通大学 医学院 1.附属第九人民医院心内科，上海 200011；2.附属瑞金医院心内科，上海 200025
  • 出版日期:2017-05-28 发布日期:2017-05-31
  • 通讯作者: 刘艳，电子信箱：liuyan_ivy@126.com。
  • 作者简介:查晴（1985—），女，主管技师，硕士生；电子信箱：zhaqing10606@163.com。曹丽娟（1988—），女，住院医师，硕士生；电子信箱：caolijuanqq@163.com。*并列第一作者。

Molecular mechanism of oxLDL inducing lipid accumulation and inflammation in macrophages to promot atherosclerosis via TLR4 signaling pathway

ZHA Qing1, CAO Li-juan1*，WANG Yan-ping2, YANG Ke2, LIU Yan1   

  1. 1.Department of Cardiology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China; 2.Department of Cardiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
  • Online:2017-05-28 Published:2017-05-31

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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。 oxLDL刺激巨噬细胞，可促进细胞中脂质累积（P<0.01）并导致oxLDL相关受体CD36和LOX-1的表达上调以及炎症因子表达（P<0.01）。特异性siRNA敲除
TLR4可抑制oxLDL诱导的巨噬细胞内脂质累积（P<0.01）和炎症因子分泌（P<0.01），并影响oxLDL诱导的CD36表达，但对LOX-1表达没有影响。结论 · oxLDL/ 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。

关键词: TLR4, 巨噬细胞, 脂质累积, 炎症反应, 动脉粥样硬化

Abstract:

Objective · To investigate the possible role of TLR4 signaling pathway in the mediation of atherosclerosis. Methods · TLR4 were knocked down via transfection with TLR4-specific siRNA, and the lipid accumulation was further detected in control and TLR4-knockdown groups by oil red O staining. The expression of CD36 and Lectin-like oxLDL receptor 1 (LOX-1) in macrophages were detected by Western blotting to investigate the role of TLR4 in the expression of oxLDL-related receptors. Cytokines such as interleukin-6 (IL-6), IL-8, monocyte chemoattractant protein 1 (MCP-1), and matrix metalloproteinase-9 (MMP-9) were tested by ELISA to confirm the possible role of TLR4 in the secretion of inflammatory factors. Results · Macrophages
(namely CD68+ cells) were found to accumulate within atherosclerosis plaques with TLR4 highly expressed on the surface of macrophages; the stimulation with oxLDL promoted the lipid accumulation (P<0.01), the secretion of inflammatory factors (P<0.01), and the expression of CD36 and LOX-1. The oxLDL-associated expression of CD36 was decreased but the expression of LOX-1 was not affected. The knockdown of TLR4 inhibits oxLDL-induced lipid accumulation (P<0.01)and inflammatory cytokines (IL-6, IL-8, MCP-1 and MMP-9) secretion (P<0.01). Conclusion · TLR4 signaling pathway possibly promotes the lipid accumulation and the secretion of inflammatory factors via up-regulating the expression of CD36 to affect the formation and development of atherosclerosis.

Key words: TLR4, macrophage, lipid accumulation, inflammation, atherosclerosis