中文摘要：

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（0.1～10 μmol/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。

英文摘要：

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.