激活素A及卵泡抑素对大鼠肾间质成纤维细胞分泌羟脯氨酸及Ⅳ型胶原的影响

Effects of activin and follistatin on hydroxyproline and type Ⅳ collagen secreted by cultured rat renal interstitial fibroblasts

目的研究激活素A(activinA,ACT-A)及卵泡抑素(follistatin,FS)在肾间质纤维化中的作用。方法SD大鼠肾间质成纤维细胞体外培养后分为A组、F组、A+F组,分别向培养液中加入ACT-A、FS、ACT-A+FS,用ELISA法检测培养液上清中羟脯氨酸(hydroxyproline,HYP)及Ⅳ型胶原(Ⅳ-C)的含量。结果在本研究浓度范围内,ACT-A浓度越高,培养液中HYP及Ⅳ-C浓度也越高;单纯加入FS对大鼠肾间质成纤维细胞分泌HYP及Ⅳ-C没有显著影响(P>0.05),但以剂量依赖方式抑制ACT-A促大鼠肾间质成纤维细胞分泌HYP及Ⅳ-C的作用(P<0.01)。结论ACT-A可能在肾间质损害的发生、发展中起重要作用,补充外源性的FS有可能为治疗肾间质纤维化提供新的思路。

Objective To investigate the roles of activin A （ACT-A） and follistatin （FS） in renal interstitial fibrosis. Methods Renal interstitial fibroblasts were isolated from SD rat kidney and primarily cultured. The cells were divided into A group, F group and A ＋ F group, and then each group was further divided into 5 subgroups according to their culture media being added with ACT-A （0, 0.3, 3, 30, or 100 ng/ml）, FS （0, 0.3, 3, 30, or 100 ng/ml）, and ACT-A （30 ng/ml） plus FS （0, 0.3, 3, 30, or 100 ng/ml） respectively. Levels of type Ⅳ collagen （Ⅳ-C） and hydroxyproline （HYP） in the supernatants of cultured fibroblasts were measured by ELISA assay. Results Concentrations of Ⅳ-C and HYP in cultured rat renal interstitial fibroblasts were in a dose-dependent manner with ACT-A treatment. FS had no effect on these concentrations, but it inhibited the effects of ACT-A on Ⅳ-C and HYP in the supernatants of cultured fibroblasts in a dose-dependent manner. Conclusion ACT-A might be involved in occurrence and development of renal fibrosis by affecting renal interstitial fibroblasts. Exogenous FS could suppress the effects of ACT-A on the cultured renal fibroblasts.