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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。
AIM: To observe the effects of resveratrol on the proliferation and apoptosis of rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS) induced by TNF-α, and to explore its effect on the PI3K / Akt / BAD signaling pathway. Methods: MTT assay was used to determine the inhibitory effect of Res on the growth of RA FLS induced by TNF-α. Flow cytometry was used to detect the effect of Res on the cell cycle and apoptosis rate of RA FLS cells. The effect of Res on TNF-α-induced phosphorylated Akt protein and its downstream effector phosphorylated BAD protein in RA FLS was analyzed by Western-blot. Results: Res inhibited the proliferation of RA FLS induced by TNF-α in a dose-and time-dependent manner. With the increase of Res concentration, the apoptosis rate of RA FLS increased, the number of cells in G0 / G1 phase increased, and the cells in G2 / M phase and S phase decreased. Compared with TNF-α group, the difference was statistically significant (P <0.05). Res inhibited TNF-α-induced RA FLS phosphorylation Akt protein and phosphorylated BAD protein expression. Conclusion: Res can inhibit the proliferation and induce the apoptosis of RA FLS cells by down-regulating the Akt phosphorylation level of PI3K / Akt signaling pathway. Res has the potential value of treating RA.