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目的探讨N-乙酰基-丝氨酰-天门冬酰-赖氨酰-脯氨酸(AcSDKP)对转化生长因子-β1(TGF-β1)介导的大鼠心脏成纤维细胞增殖与胶原代谢的调节作用。方法采用差速贴壁法获取新生大鼠心脏成纤维细胞;3H-TdR掺入法检测心脏成纤维细胞的增殖,免疫细胞化学染色法检测增殖细胞核抗原(PCNA)的表达。3H-脯氨酸掺入法检测心脏成纤维细胞胶原蛋白的合成,Western blot法检测Ⅰ、Ⅲ型胶原蛋白与MMP-1、TIMP-1蛋白的表达。结果AcSDKP抑制了TGF-β1对心脏成纤维细胞MMP-1蛋白表达的下调作用,使MMP-1蛋白表达增加,而对TGF-β1介导的TIMP-1蛋白表达无明显影响,使MMP-1/TIMP-1比值增加。结论AcSDKP抑制TGF-β1介导的心脏成纤维细胞的增殖、胶原合成,上调MMP-1蛋白表达,使MMP-1/TIMP-1比值增加,这可能与AcSDKP抗心脏纤维化的作用相关。
Objective To investigate the effects of AcSDKP on the proliferation and collagen metabolism of rat cardiac fibroblasts induced by transforming growth factor-β1 (TGF-β1) Regulatory effect. Methods Cardiac fibroblasts of newborn rats were obtained by differential adherence method. Proliferation of cardiac fibroblasts was detected by 3H-TdR incorporation method. The expression of proliferating cell nuclear antigen (PCNA) was detected by immunocytochemical staining. 3H-proline incorporation assay was used to detect collagen synthesis in cardiac fibroblasts. The expressions of type I, type III collagen and MMP-1, TIMP-1 protein were detected by Western blot. Results AcSDKP inhibited the down-regulation of MMP-1 protein expression in cardiac fibroblasts induced by TGF-β1 and increased the expression of MMP-1 protein but not TGF-β1-mediated TIMP-1 protein expression. / TIMP-1 ratio increased. Conclusion AcSDKP can inhibit the proliferation and collagen synthesis of cardiac fibroblast induced by TGF-β1 and up-regulate the expression of MMP-1 and MMP-1 / TIMP-1, which may be related to the anti-cardiac fibrosis effect of AcSDKP.