辛伐他汀抑制脂肪细胞ox-LDL诱导的内质网应激与炎性脂肪因子分泌

吴智鸿; 陈雅琴; 赵水平

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辛伐他汀抑制脂肪细胞ox-LDL诱导的内质网应激与炎性脂肪因子分泌

首发时间：2013-01-15

吴智鸿 ¹
吴智鸿(1977-),男，主治医师，主要从事血脂与动脉粥样硬化研究。
陈雅琴 ¹ 赵水平 ¹

1、中南大学湘雅二医院心血管内科，长沙 410011

摘要：目的：探讨辛伐他汀对3T3-L1脂肪细胞氧化低密度脂蛋白(ox-LDL)诱导的内质网应激与炎性脂肪因子分泌的影响；方法：将分化成熟的3T3-L1脂肪细胞分别与不同浓度的ox-LDL(0至100μg/ml)、4-苯基丁酸(4-PBA)(0至20 mM)＋ox-LDL(50μg/ml)及辛伐他汀(0至10μmol/L)＋ox-LDL(50μg/ml)孵育24小时，用western blot法检测内质网应激标志物糖调节蛋白78（GRP78）及C/EBP同源蛋白(CHOP)的蛋白表达，用real-time PCR法检测炎性脂肪因子肿瘤坏死因子-α(TNF-α)与单核细胞趋化蛋白-1(MCP-1)的mRNA表达，用ELISA法检测上清液TNF-α与MCP-1的分泌量；结果：ox-LDL剂量依赖性地上调GRP-78与CHOP的蛋白表达，并刺激TNF-α与MCP-1的mRNA表达与分泌；4-PBA与辛伐他汀均能抑制ox-LDL诱导的内质网应激标志物表达，并减少TNF-α与MCP-1的mRNA表达与分泌，其作用呈剂量依赖性。结论：ox-LDL通过诱导内质网应激刺激脂肪细胞TNF-α与MCP-1的表达与分泌，辛伐他汀可能通过抑制内质网应激而在脂肪细胞上发挥抗炎作用。

关键词：内科学脂肪细胞辛伐他汀内质网应激炎症

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Simvastatin inhibits ox-LDL-induced inflammatory adipokines secretion via amelioration of ER stress in 3T3-L1 adipocyte

Wu Zhihong ¹
吴智鸿(1977-),男，主治医师，主要从事血脂与动脉粥样硬化研究。
Chen Yaqin ² Zhao Shuiping ³

1、Department of Cardiology, the Second Xiangya Hospital of Central South University,Changsha 410011
2、Department of Cardiology,the Second Xiangya Hospital of Central South University,Changsha 410011
3、Department of Cardiology, the Second Xiangya Hospital of Central South University, Changsha 410011

Abstract：Objective: To explore the effect of simvastatin on the ox-LDL-induced endoplasmic reticulum stress and inflammatory adipokines secretion in 3T3-L1 adipocytes. Method: Differentiated adipocytes were treated with various concentrations of ox-LDL (0 to 100μg/ml); 4-phenylbutyrate (4-PBA)(0 to 20 mM)+ox-LDL(50μg/ml); simvastatin(0 to 10μmol/L)+ox-LDL(50μg/ml) for 24 hours. The protein expressions of ER stress markers, glucose-regulated protein 78 (GRP78) and C/EBP homology protein (CHOP), were determined by western blot analysis. The mRNA expressions of inflammatory adipokines, tumor necrosis factor-α (TNF-α) and monocyte chemoattractant protein 1 (MCP-1) were measured by real-time PCR. The protein secretion of TNF-α and MCP-1 in culture medium were evaluated by ELISA. Results: ox-LDL treatment led to significant up-regulation of GRP78 and CHOP in dose-dependent manner. The expressions of TNF-α and MCP-1 were dose-dependently increased at mRNA and protein levels after ox-LDL intervention. Both 4-PBA and simvastatin could ameliorate ox-LDL-induced ER stress and reduce the expression of TNF-α and MCP-1 at mRNA and protien level in dose dependent manner. Conclusions: Ox-LDL stimulated the expression and secretion of TNF-α and MCP-1 through its activation of ER stress in adipocytes. Simvastatin might exert direct anti-inflammatory effects in adipocytes through inhibition of ER stress.

Keywords： Internal medicine；Adipocyte；Simvastatin；Endoplasmic reticulum stress；Inflammation

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吴智鸿，陈雅琴，赵水平. 辛伐他汀抑制脂肪细胞ox-LDL诱导的内质网应激与炎性脂肪因子分泌[EB/OL]. 北京：中国科技论文在线 [2013-01-15]. https://www.paper.edu.cn/releasepaper/content/201301-670.

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论文编号	201301-670
论文题目	辛伐他汀抑制脂肪细胞ox-LDL诱导的内质网应激与炎性脂肪因子分泌
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