阿托伐他汀对HMGB1诱导血管内皮细胞激活的影响  

Effect of Atorvastatin on Vascular Endothelial Activation Induced by HMGB1

作　　者：李馨欣[1,2] 杨俊[1,2] 杨简[1,2] 丁家望[1,2] 李松[1,2] 董武松[1,2] 

机构地区：[1]三峡大学心血管病研究所 [2]三峡大学第一临床医学院心内科,湖北省宜昌市443000

出　　处：《中国动脉硬化杂志》2013年第3期193-197,共5页Chinese Journal of Arteriosclerosis

基　　金：国家自然科学基金资助项目(81170133);湖北省自然科学基金计划项目(2011CDB179)

摘　　要：目的探讨阿托伐他汀能否抑制高迁移率族蛋白1(HMGB1)诱导的血管内皮细胞激活,阐明其潜在的分子机制。方法体外培养大鼠胸主动脉内皮细胞,分别用不同浓度的阿托伐他汀、HMGB1、TLR4特异性抑制剂CLI-095预处理内皮细胞,荧光定量分析中性粒细胞与内皮细胞的黏附活力;实时定量RT-PCR与Western blot分别检测TLR4、细胞间黏附分子1(ICAM-1)和E-选择素mRNA和蛋白的表达水平;电泳迁移率实验(EMSA)测定核因子κB(NF-κB)p65的DNA结合活性。结果阿托伐他汀(0.1～10μmol/L)呈剂量依赖性地抑制HMGB1诱导的血管内皮细胞活化。阿托伐他汀预处理能明显下调HMGB1诱导的TLR4 mRNA和蛋白表达水平(P均<0.05);阿托伐他汀、CLI-095均能有效抑制HMGB1诱导的NF-κB p65的DNA结合活性以及ICAM-1和E选择素的表达水平(P均<0.05)。结论阿托伐他汀可通过调节黏附分子(ICAM-1和E-选择素)的表达而显著抑制HMGB1诱导的血管内皮细胞活化效应,其机制可能与它抑制TLR4的表达及NF-κB激活有关。Aim To explore whether atorvastatin inhibits HMGB1-induced vascular endothelial activation, and clarify the underlying molecular mechanism. Methods The cultured endothelial cells （EC） of rats were treated by Atorvastatin, HMGB1,TLR4-specific inhibitor CLI-095 with different concentrations. Leukocyte-endothelial adhesion was calculated as the proportion of the adherent neutrophils fluorescence intensity among the total added cells. RT-PCR and Western blot method were used to assay the expression of Toll like receptor 4（TLR4）, ICAM-1 , E-selectin mRNA and protein. DNA binding activity of NF-κB was measured by EMSA. Results Atorvastatin, at concentrations ranging from 0.1 to 10 μmol/L, effectively and in a dose-dependent manner inhibited HMGB1-induced ECs activation. Atorvastatin markedly suppressed TLR4 expression （P〈0.05） in ECsIncubation of ECs with atorvastatin and CLI-095 reduced HMGB1-induced NF-κB p65 DNA binding activity and adhesion molecules （ICAM-1 and E-selectin） expression （P〈0.05）. Conclusion Atorvastatin can attenuate HMGB1-induced vascular endothelial activation. The underlying mechanism may be connected with inhibition of TLR4/NF-κB-dependent signaling pathway induced leukocyte-endothelial adhesion.

关 键 词：高迁移率族蛋白1 阿托伐他汀 内皮细胞 TOLL样受体4 

分 类 号：R363[医药卫生—病理学]