雷公藤甲素抑制TGF—β1的促皮肤成纤维细胞增殖效应的实验研究  

Triptolide inhibits proliferation of dermal fibroblasts promoted by TGF-β^1

作　　者：朱金土[1] 杨晓红[1] 余土根[1] 曹毅[1] 

机构地区：[1]浙江中医药大学附属第一医院整形科,杭州310006

出　　处：《浙江医学》2009年第3期292-294,297,共4页Zhejiang Medical Journal

摘　　要：目的 观察雷公藤甲素抑制转化生长因子-β^1（TGF-β^1）促皮肤成纤维细胞增殖的作用并阐明其作用机制。方法用MTT法分别检测不同浓度外源性TGF—β^1及雷公藤甲素作用下皮肤成纤维细胞增殖的情况以及10^-7mol／L雷公藤甲素对25ng／mlTGF—β^1引起的皮肤成纤维细胞增殖的影响；蛋白免疫印迹法检测10^7mol／L的雷公藤甲素和25ng／ml的TGF—β^1、作用下皮肤成纤维细胞ERK1／2的磷酸化情况。结果TGF—β^1促进皮肤成纤维细胞的增殖呈浓度依赖性，而雷公藤甲素抑制皮肤成纤维细胞增殖也呈浓度依赖性；10^-8mol／L的雷公藤甲素即可抑制皮肤成纤维细胞增殖（P〈0．01），10^-7mol／L的雷公藤甲素基本达到最大的效应（P〈0.01）。10^-7mol／L雷公藤甲素可以显著抑制25ng／ml的TGF-β^1对皮肤成纤维细胞的促增殖作用及对ERK1／2促磷酸化作用。结论雷公藤甲素能够抑制TGF—β^1对皮肤成纤维细胞的促增殖作用。Objective To determine the inhibition effect and possible mechanism of triptolide on the proliferation of dermal fibroblasts promoted by TGF-β^1 1. Methods Cultured dermal fibroblasts were treated by TGF-β^1 （0, 1, 5, 10, 25, 50, 100 and 200 ng/ml）or triptolide （0, 10 9, 104, 10 7 104 and 10 s mol/L）, the cell proliferation was determined by MTT assay. Dermal fibroblasts were also treated by TGF-β^1 （25ng/ml） combined with triptolide （10^-7 mol/L）, and the phosphorylation of ERK1/2 with or without pretreatment of triptolide （10^-7 mol/L） was detected by Western blotting assay. Results TGF-β^1 enhanced the proliferation of dermal fibroblasts in a dose-dependent manner; and triptolide inhibited the proliferation of dermal fibroblasts also in a dose-dependent manner. Compared with control group, 10^-4 mol/L triptolide inhibited the proliferation of dermal fibroblasts significantly （P≤0.01）, while if the dose was higher than 10^-7 mol/L, triptolide induced cell apoptosis and necrosis. 10 7 mol/L triptolide effectively inhibited the proliferation of dermal fibroblasts induced by 25ng/ml TGF- 13 1 （P≤0.01）. 25ng/ml TGF- β 1 induced the phosphorylation of ERK1/2 in dermal fibroblasts, but this effect was diminished in the cells pretreated with 10^-7 mol/L triptolide for lh. Conclusion Triptolide can inhibit the proliferation of dermal fibroblasts promoted by TGF- β^1, which is associated with the inhibition of phosphorylation of ERK1/2.

关 键 词：皮肤成纤维细胞 雷公藤甲素 TGF—β^1 

分 类 号：R329.28[医药卫生—人体解剖和组织胚胎学] R285.5[医药卫生—基础医学]