丙酮酸乙酯对滑膜细胞HMGB1的影响及机制

目的 探讨丙酮酸乙酯对类风湿关节炎（RA）滑膜细胞高迁移率族蛋白-1（HMGB1）表达的影响及分子机制.方法 将培养的RA滑膜细胞分为正常对照组、TNF-α组和丙酮酸乙酯＋TNF-α组;采用RT-PCR法检测细胞HMGB1 mRNA表达;ELISA法检测细胞培养上清液中HMGB1、IL-6和IL-8含量;采用Western blot法分别检测滑膜细胞胞质和核内NF-κB变化;采用免疫荧光法观察NF-κB在细胞中的分布.结果 丙酮酸乙酯可抑制TNF-α诱导滑膜细胞IL-6、IL-8、HMGB1的分泌和HMGB1 mRNA的表达,以及NF-κ B（p65）在滑膜细胞核内的表达和移位.结论 丙酮酸乙酯能下调滑膜细胞HMGB1表达和抑制NF-κB信号通路活化,可能对RA发挥抗炎作用.

Effect of ethyl pyruvate on expression of HMGB1 in synoviocytes of rheumatoid arthritis

Objective To investigate the effects of ethyl pyruvate （EP） on the expression of high mobility group box chromosomal protein 1（HMGB1） in synoviocytes of rheumatoid arthritis（RA） and its molecular mechanism.Methods RA synoviocytes were cultured and divided into normal control group,TNF-a group,EP＋TNF-α group.The expression of HMGB1 mRNA in cultured synoviocytes was determined by RT-PCR.HMGB1 concentrations in culture supernatants were measured with enzyme-linked immunosorbent assays （ELISA）.Nuclear translocation of NF-κ B was examined by Western blotting and immunohistochemistry.Results EP down-regulated HMGB1 mRNA expression and secretion in RA synoviocytes induced by TNF-a.EP inhibited nuclear translocation of NF-κ B in RA synoviocytes induced by TNF-α.Conclusion EP has an anti-inflammatory effect on RA by down-regulation of HMGB1 in synoviocytes,which may be associated with inhibiting the activation of NF-κ B signal pathways.