过氧化物酶体增殖物激活受体γ激动剂对转化生长因子β1诱导皮肤成纤维细胞作用的影响

目的 观察过氧化物酶体增殖物激活受体γ(PPARγ)激动剂对转化生长因子(TGF)-β1诱导成纤维细胞(Fb)转分化及对胶原牛成作用的影响.方法 体外培养成人正常皮肤Fb,免疫荧光细胞化学法观察PPARγ配体15-脱氧前列腺素J2(15d-PGJ2)、曲格列酮对TGF-β1诱导的α平滑肌动蛋白(α-SMA)表达的影响,Western blot检测15d-PGJ2、曲格列酮对TGF-β1诱导的α-SMA及Ⅰ型胶原蛋白表达的影响,噻唑蓝(MTT)比色法观察对Fb增殖活性的影响.结果 与TGF-β1诱导组比较,10μmoL/L曲格列酮、10 μmol/L 15d-PGJ2预处理组的α-SMA表达量显著减少(P<0.01),抑制效应分别为31%、57%;预处理组的Ⅰ型胶原表达量也屁著减少(P<0.01),抑制效应分别为57%、38%.曲格列酮、15d-PGJ2对Fb的增殖活性影响分析,各实验组与对照组比较差异无统计学意义(P>0.05).结论 PPARγ激动剂能抑制TGF-β1诱导的人正常皮肤Fb的转分化和Ⅰ型胶原合成增多的效应,具有抗瘢痕的潜在作用.

Effects of peroxisome prolilerator-activated receptor γ agonists on transforming growth factor-β1 induced profibrotic activities in normal skin fibroblasts in vitro

Objective To observe the effects of peroxisome prolilerator-activated receptorγ(PPARγ) agonists on TGF-β1-induced transdifferentiation and collogen production of the cultured normal skin fibroblasts in vitro. Methods In cultured normal skin fibroblasts, the effects of both natural ( 15d-PGJ2) and synthetic (troglitazone) PPARγ agonists on the level of TGF-β1-indued α-SMA expression were assessed by immuuofluoreseence. The effects of PPARγ/agonists on the level of α-SMA and collagen type Ⅰ expression induced by TGF-βI were detected by Western blot. The MTT was employed to measure the fibroblasts proliferation after fibroblasts were treated by troglitazone and 15d-PGJ2. Results The level of α-SMA protein expression in troglitazone and 15d-PGJ2-pretreated groups respectively was significantly decreased by 31% and 57% respectively as compared with TGF-β1-stimulated group (P<0.01). TGF-131 caused an obvious increase in the levels of cellular type Ⅰ collagen, but pretreatment with troglitazone or 15d-PGJ2 reduced this stimulation by 57% and 38%, respectively. In cell viability, there was no signifi-cant difference between the experimental groups and the control group (P>0.05). Conclusion PPARγ agonists may inhibit profibrotic activities of TGF-β1 on skin fibroblasts,suggestig they have novel and potent antifibrotic effects in human skin fibroblasts.