N-乙酰基-丝氨酰-天门冬酰-赖氨酰-脯氨酸对转化生长因子β_1介导的心成纤维细胞MMP-1/TIMP-1表达的调节作用  

Effect of N-acetyl-seryl-aspartyl-lysyl-proline on the expression of MMP-1/TIMP-1 in cultured cardiac fibroblast mediated by TGF-β_1

作　　者：王小君[1] 杨方[1] 刘丽[1] 吴芳[1] 王瑞敏[1] 马文东[1] 罗玲[1] 户万秘[1] 裴新[1] 张丽娟[1] 

机构地区：[1]华北煤炭医学院实验研究中心,唐山063000

出　　处：《解剖学杂志》2007年第5期558-561,共4页Chinese Journal of Anatomy

基　　金：河北省科技厅博士基金(04547002D-5);河北省教育厅基金(2003112);唐山市新医药基础研究重点实验室项目(04362001B-9)

摘　　要：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β_1(TGF-β_1)介导的大鼠心成纤维细胞MMP-1/TIMP-1的调节作用。方法:差速贴壁法分离与获取新生大鼠心成纤维细胞。分别采用免疫细胞化学法和Western印迹法检测心成纤维细胞MMP-1、TIMP-1蛋白表达。结果:TGF-β_1可使心成纤维细胞MMP-1蛋白表达水平下降,而促进TIMP-1蛋白表达,MMP-1/TIMP-1比值下降。AcSDKP可以抑制TGF-β_1对心成纤维细胞MMP-1表达的下调作用,使MMP-1蛋白表达增加,而对TGF-β_1介导的TIMP-1蛋白表达无明显影响,MMP-1/ TIMP-1比值增加。结论:AcSDKP可以通过上调TGF-β_1介导的心成纤维细胞MMP-1蛋白表达并增加MMP-1/ TIMP-1比值,以加速细胞外基质降解,这可能与AcSDKP抗心纤维化的作用有关。Objective： To investigate whether N-acetyl-seryl-aspartyl-lysyl-proline （AcSDKP） can regulate MMP-1 and TIMP-1 expression mediated by TGF-β1 in cultured rat cardiac fibroblasts. Methods： Neonatal cardiac fibroblasts were isolated in rats, The expressions of MMP-1 and TIMP-1 were detected with Western blot and immunocytochemistry. Results： TGF-β1 decreased the expression of MMP-1 and enhanced that of TIMP-1 in cardiac fibroblasts. The ratio of MMP-1/TIMP- 1 was depressed. AcSDKP increased MMP-1 expression by inhibiting the down-regulation effect of TGF-β1, but had no effect on TIMP-1 expression in cardiac fibroblasts. The ratio of MMP-1/TIMP-1 was increased. Conclusion： AcSDKP can promote degradation of extracellular matrix by increasing the expression of MMP-1 and ratio of MMP-1/TIMP- 1 mediated by TGF-β1 in cardiac fibroblasts, which is possibly related with the anti-fibrosis effect of AcSDKP.

关 键 词：N-乙酰基-丝氨酰-天门冬酰-赖氨酰-脯氨酸 转化生长因子Β1 心成纤维细胞 基质金属蛋白酶 基质金属 蛋白酶组织抑制因子 

分 类 号：R363[医药卫生—病理学]