抗纤维化短肽N-乙酰基-丝氨酰-天门冬酰-赖氨酰-脯氨酸对大鼠心脏成纤维细胞胶原合成与降解的调节作用  

Role of AcSDKP on collagen synthesis and degradation in cultured rat cardiac fibroblast

作　　者：杨方[1] 朱曦龄[1] 王丽平[1] 宋旭东[1] 王瑞敏[1] 李治国[1] 罗玲[1] 户万秘[1] 马文东[1] 裴鑫[1] 张丽娟[1] 李琪佳[1] 

机构地区：[1]华北煤炭医学院实验研究中心,唐山063000

出　　处：《中华心血管病杂志》2006年第9期843-846,共4页Chinese Journal of Cardiology

基　　金：河北省科博士基金(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资助项目(04362001B)

摘　　要：目的探讨N-乙酰基-丝氨酰-天门冬酰-赖氨酰-脯氨酸（AcSDKP）对血小板源性生长因子（PDGF）诱导的大鼠心脏成纤维细胞增殖、胶原合成和降解代谢的调节作用。方法分离培养新生大鼠心脏成纤维细胞。采用^3H-TdR和。H-脯氨酸掺入法分别检测心脏成纤维细胞增殖与胶原蛋白合成。Western blot法检测心脏成纤维细胞Ⅰ、Ⅲ型胶原蛋白表达和基质金属蛋白酶（MMP）-1蛋白的表达。明胶酶谱法检测心脏成纤维细胞MMP-2和MMP-9活性的表达。结果PDGF促进心脏成纤维细胞增殖、胶原合成，Ⅰ、Ⅲ型胶原表达，以及MMP-2、MMP-9活性和MMP-1表达。AcSDKP对PDGF介导的心脏成纤维细胞增殖、胶原合成均有抑制作用。AcSDKP上调由PDGF介导的心脏成纤维细胞MMP-2、MMP-9活性和MMP-1的表达。结论AcSDKP抑制PDGF介导的心脏成纤维细胞增殖和胶原的合成，上调MMPs活性或表达，促进胶原的降解，这些可能与AcSDKP抗心脏纤维化作用相关。Objective To investigate the role of AcSDKP on collagen synthesis and degradation in cultured rat cardiac fibroblasts. Methods Neonatal rat cardiac fibroblasts were isolated and stimulated by PDGF. The cell proliferation was observed by ^3 H-TdR incorporation assay. The synthesis of collagen was measured by ^3H-proline incorporation assay. The expression of type Ⅰ and type Ⅲ collagen and MMP-1 protein were measured by Western blot. The MMP-2 and MMP-9 activity was evaluated with zymography assay. Results PDGF stimulated cardiac fibroblasts proliferation with increased collagen synthesis and type Ⅰ and type Ⅲ collagen protein expressions as well as MMP-2 and MMP-9 activities and MMP-1 expression. AcSDKP inhibited cardiac fibroblasts proliferation induced by PDGF and reduced collagen synthesis and type Ⅰ and type Ⅲ collagen protein expression. AcSDKP also further up-regulated MMP-2 and MMP-9 activities and MMP-1 expression in cardiac fibroblasts induced by PDGF. Conclusion AcSDKP inhibited proliferation and collagen synthesis and up-regulated matrix metalloproteinases activity or expression induced by PDGF, which was possibly related with the effect of AcSDKP anti-fibrosis.

关 键 词：成纤维细胞 肽类 血小板源性生长因子 基质金属蛋白酶 

分 类 号：R541[医药卫生—心血管疾病]