目的: 研究N-乙酰基-丝氨酰-天冬氨酰-赖氨酰-脯氨酸(N-acetyl-seryl-aspartly-lysyl-proline, AcSDKP)对转化生长因子β1(Transforming growth factor beta 1, TGF-β1)诱导大鼠骨髓间充质干细胞(mesenchymal stem cells, MSCs)向肌成纤维细胞(myofibroblast, MF)分化的影响, 探讨 AcSDKP抗纤维化作用的可能机制。方法: 全骨髓贴壁法分离培养大鼠骨髓MSCs。使用免疫组化, Western blotting技术分析α-SMA蛋白的表达以及Smad2/3, ERK1/2蛋白磷酸化的变化情况。结果: 和对照组相比, TGF-β1诱导的MSC中α-SMA、磷酸化-Smad2/3及磷酸化-ERK1/2的表达大大增强, 使用AcSDKP干预细胞则三者的表达量明显下降且呈一定的剂量依赖性。结论: AcSDKP可以显著抑制TGF-β1诱导的大鼠MSCs向MF分化, 可能通过抑制TGF-β/Smad/ERK1/2信号通路的激活, 从而发挥其抗器官纤维化作用。

Objective:To investigate the effects of antifibrotic peptide N-acetyl- seryl-aspartly-lysyl-proline (AcSDKP) on the differentiation of rat MSCs into myofibroblasts mediated by transforming growth factor beta- 1(TGF-β1). To explore the possible anti-fibrotic mechanisms of AcSDKP in depth. Methods:Isolated the mesenchymal stem cells (MSCs) by the whole bone marrow culture method. The protein expressions of α-SMA and the changes of phospho- Smad2/3 and phospho- ERK1/2 were detected by immunocytochemistry and Western blotting. Results:Compared with the control group, the protein expressions of α-SMA, p-Smad2/3, p-ERK1/2 were greatly increased in MSCs which was induced by TGF-β1, and showed a dose-dependent decrease in AcSDKP group. Conclusion: AcSDKP markedly inhibit the differentiation of rat MSCs into myofibroblasts probably by blocking the TGF-β/Smad/ERK1/2 signaling pathway activation, and thus mediating its anti fibrosis activity.