GDF11逆转oxLDL对于巨噬细胞中胆固醇逆转运相关分子的抑制及炎症因子上调的机制和功能研究

项目名称： GDF11逆转oxLDL对于巨噬细胞中胆固醇逆转运相关分子的抑制及炎症因子上调的机制和功能研究

项目编号： No.81503064

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 张玲

作者单位： 中国人民解放军第四军医大学

项目金额： 17.9万元

中文摘要： GDF11是分泌型转化生长因子b（TGFb）超家族信号分子，LXR是配体激活的转录因子，ABCA1/G1通过调控巨噬细胞胆固醇的外输抑制脂质堆积，CD36作为oxLDL受体介导胆固醇的内流促进巨噬细胞的泡沫化。我们前期工作发现：GDF11可以有效诱导巨噬细胞ABCA1/G1的表达，同时GDF11可以有效逆转oxLDL对于ABCA1/G1的抑制和对于CD36的诱导，揭示了GDF11在巨噬细胞泡沫化和胆固醇逆转运中可能发挥着重要作用；同时GDF11可以有效抑制oxLDL对于炎症因子IL-1、IL-6、MMP9的诱导，使其降低到正常对照组水平，揭示了GDF11可能会发挥抗炎作用。在机制上阐明GDF11活性对于巨噬细胞胆固醇逆转运功能和表型的影响；明确LXR对于GDF11的表达调控机制；在细胞和动物水平探讨GDF11是否具有防治动脉粥样硬化的作用。

中文关键词： 生长转化因子11；动脉粥样硬化；巨噬细胞

英文摘要： GDF11 is a member of TGFb famaly. LXRs are ligand activated nuclear receptor.ABCA1 and ABCG1 can mediate the efflux of cholesterol to outside apoAI and HDL. CD36 act as oxLDL receptor can mediate the influx of oxLDL. We found that GDF11 can promote the expression of ABCA1/G1. Meanwhile GDF11 can reverse the inhibition effect of oxLDL on ABCA1/G1 expression and inhibit the upregulation of CD36 by oxLDL. Macrophage can be devided into two phenotype:MI and MII. MI can produce proinlammatory cytokines，such as IL-1、IL-6、TNFa. And GDF11 can inhibit the induction effect of oxLDL on MI proinlammatory cytokines’ production. It indicate that GDF11 may influence the reverse cholesterol transportation fuction of macrophage and the transition of MI to MII. We want to find the effect of GDF11 on macrophage cholesterol efflux and how LXRs regulate GDF11 expression. Whether GDF11 can promote the transition of MI to MII. To explore the effect of GDF11 on AS formation and provide a new target for the cure of atherosclerosis.

英文关键词： GDF11;Atherosclerosis;Macrophage