摘要
目的研究金雀异黄素(Genistein,Gen)对类风湿关节炎(rheumatoid arthritis,RA)动物模型CIA大鼠成纤维样滑膜细胞(fibroblast-like synoviocytes,FLS)增殖、凋亡及其PI3K/AKT信号转导通路的影响。方法采用0、50、100、200μmol.L-1的Gen处理FLS 24、48、72 h,采用MTT法检测Gen对FLS增殖的影响;免疫印迹(Western blot)法检测Gen对CIA大鼠FLS凋亡蛋白bcl-2、bax表达的影响;West-ern blot法检测不同浓度的Gen处理后的CIA大鼠FLS中AKT和p-AKT表达情况。结果 50、100、200μmol.L-1的Gen均能抑制CIA大鼠FLS的增殖,且能够调节CIA大鼠FLS凋亡蛋白的表达,呈剂量依赖性关系;Gen对细胞中AKT蛋白表达无影响,不同浓度的Gen作用于FLS 72 h后p-AKT表达均有降低(P<0.05)且随Gen浓度的增加p-AKT表达逐渐降低。结论 Gen能够调节CIA大鼠FLS增殖与凋亡的平衡,其作用机制可能与下调PI3K/AKT信号传导通路的酪氨酸激酶,抑制AKT的磷酸化有关。
Aim To investigate the effects of Genistein（Gen） on the proliferation and apoptosis of fibroblast-like synoviocytes（FLS） from rats with collagen Ⅱinduced arthritis（CIA）.Methods MTT assay was performed to study the effect of Gen on FLS proliferation.Different concentrations of Gen（50,100,200 μmol·L-1）were given to the incubation with FLS and Western blotting assay was used to test the effect of Gen on the expression of bcl-2,bax,AKT,p-AKT in FLS.Results MTT assay showed that the proliferation of FLS in CIA rats treated with different concentrations of Gen（50,100,200 μmol·L-1） was inhibited significantly（P0.05） in a dose-dependent manner.Western blot analysis showed that different concentrations of Gen increased expression of bax protein in a dose-dependent manner.Meanwhile,the different concentrations of Gen（50,100,200 μmol·L-1） also significantly reduced expression of bcl-2 protein（P0.05）.The expression of ERK protein in Gen treatment FLS was not significantly different（P0.05）.In 72 hour,the expression of p-ERK protein in Gen treatment groups was lower than that in model group（P0.05） in a dose-dependent inhibition with Gen concentrations.Conclusion Gen inhibits the activation of PI3K-AKT signal transduction pathways in FLS of CIA rats.Consequently,Gen may regulate the balance of proliferation and apoptosis in FLS of CIA rats through adjusting signal transduction pathways in FLS.
出处
《中国药理学通报》
CAS
CSCD
北大核心
2011年第8期1161-1165,共5页
Chinese Pharmacological Bulletin
基金
江苏省高校自然科学基础研究项目课题(No07KJD320245)
