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作 者 ：田静,高洁生,陈进伟,李芬,谢希,杜金烽,王静,毛妮

期 刊 ：中国中药杂志 2010年 35卷 14期 页码：1878.

关键词：白藜芦醇；滑膜细胞；增殖；凋亡；

Keywords:resveratrol, fibroblast-like synoviocytes, proliferation, apoptosis,

摘 要 ：目的: 观察白藜芦醇(Res)对TNF-α诱导类风湿关节炎(RA)成纤维样滑膜细胞(FLS)增殖及凋亡的影响,探讨其对PI3K/Akt/BAD信号通路作用。 方法 : MTT比色法测定Res对TNF-α诱导RA FLS生长的抑制作用。流式细胞仪检测Res对RA FLS细胞周期及凋亡率的影响。Western-blot方法分析Res对TNF-α诱导RA FLS中磷酸化Akt蛋白及其下游效应分子磷酸化BAD蛋白表达的影响。 结果 : Res对TNF-α诱导RA FLS 增殖具有抑制作用,呈时间剂量依赖性。随着Res浓度增加,RA FLS凋亡率增加,G₀/G₁期细胞增多,G₂/M期及S期细胞减少,与TNF-α组比较,差异具有统计学意义(P<0.05)。Res可抑制TNF-α诱导RA FLS磷酸化Akt蛋白以及磷酸化BAD蛋白的表达。 结论 : Res通过阻滞RA FLS细胞周期、下调PI₃K/Akt信号通路Akt磷酸化水平发挥抑制增殖、诱导凋亡作用,Res具有治疗RA的潜在价值。

Abstract:Objective : To observe the effect of resveratrol (Res) on in vitro proliferation and apoptosis of TNF-α induced rheumatoid arthritis fibroblast-like synoviocytes (RA FLS), and further to investigate the PI₃K/Akt/BAD signal mechanism. Method : The inhibition rate of RA FLS was examined by MTT assay. Cell cycle and the amount of apoptotic cells was measured by flow cytometry. PI₃K/Akt/BAD signal transduction proteins expression was measured by western blot. Result : The living cells measured by MTT dose and time-dependently reduced in Res groups. In Res groups, the fraction of living cells in the S-phase and G₂/M-phase decreased respectively, while that in G₁-phase increased, the difference was statistically significant compared with the TNF-α group (P<0.05). Flow cytometry demonstrated that the apoptosis rate increased with increased Res concentration. Res inhibited TNF-α induced phosphorylation of Akt and BAD in RA FLS. Conclusion : Res can inhibit RA FLS proliferation and induce apoptosis through inhibition of PI₃K/Akt/BAD signalling pathway. Res may provide a new therapeutic approach in treatment of RA.

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