N-乙酰基-丝氨酰-天冬氨酰-赖氨酰-脯氨酸对基质金属蛋白酶-1和基质金属蛋白酶组织抑制因子-1的调节在大鼠矽肺纤维化形成中的作用  

Effect of N-acetyl-seryl-aspartyl-lysyl-proline on expression of MMP-1 and TIMP-1 in the lung of rat with silicosis

作　　者：杨方[1] 陈萍[1,2] 王俐玻[1,3] 李倩[1] 张丽娟[1] 闫静波[1,4] 

机构地区：[1]华北煤炭医学院实验中心,唐山063000 [2]泰达心血管病医院超声科,塘沽300457 [3]华北煤炭医学院校医院,唐山063000 [4]邢台市人民医院病理科,邢台054031

出　　处：《解剖学杂志》2009年第6期719-723,共5页Chinese Journal of Anatomy

基　　金：人事部留学人员科技活动项目（国人厅发[2006]164号）;河北省自然科学基金（C2005000807）;唐山市新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-天冬氨酰-赖氨酰-脯氨酸（AcSDKP）对大鼠肺内基质金属蛋白酶-1（MMP-1）和基质金属蛋白酶组织抑制因子-1（TIMP-1）表达的调节在拮抗矽肺纤维化形成过程中的作用。方法：气管内灌注染尘法制作大鼠矽肺模型，将含有AcSDKP的微量药物释放泵埋入腹腔。实验动物随机分为矽肺模型对照4周组，矽肺模型对照8周组，矽肺模型4周组，矽肺模型8周组，抗纤维化治疗组及预防治疗组。H—E染色和免疫组织化学显色对矽肺纤维化病变和MMP-1和TIMP-1在肺组织内的表达进行形态学观察；免疫印迹法对肺内MMP-1和TIMP-1酶蛋白表达进行检测。结果：与模型对照组比较，矽肺大鼠肺内MMP-1和TIMP-1表达增强。与矽肺模型组比较，AcSDKP能够上调矽肺大鼠肺内MMP-1的表达，下调TIMP-1的表达，使MMP-1／TIMP-1的比值升高。结论：AcSDKP能够促进矽肺大鼠肺内MMP-1的表达，抑制TIMP-1的表达，从而加速了细胞外基质（包括胶原）的降解，这可能与AcSDKP抗矽肺纤维化的作用有关。Objective： To investigate the effect of N-acetyl-seryl-aspartyl-lysyl-proline （AcSDKP） on the expression of MMP- 1 and TIMP-1 in the lung of rat with silicosis. Methods： The Wistar rats were intratracheally instilled with silica as silicotic models. Drug releasing pumps with AcSDKP were implanted in the abdominal cavity of the rats. Rats were divided into 6 groups randomly： control 4 weeks, control 8 Weeks, silicotic model 4： weeks, silicotic model 8 weeks, anti-fibrosis treatment of AcSDKP and preventing fibrosis treatment of AcSDKP. The lung fibrosis and expression of MMP-1 and TIMP-1 were observed by H-E staining and immunohistochemistry; The expressions of MMP-1 and TIMP-1 protein in the lungs of the rats were evaluated by Western blot. Results： Compared with the control group, the expressions of MMP-1 and TIMP-1 were increased in the lungs of the rats with silicosis. ComPared with the silicotic model group, AcSDKP up-regulated the expression of MMP-1, down-regulated the expression of TIMP-1 in the lungs of .the rats with silicosis, and increased the MMP-1/TIMP-1 ratio. Conclusion= AcSDKP could stimulate the expression of MMP-1 and inhibit the expression of TIMP- 1 in the lungs of rats with silicosis, and thus induce the extracellular matrix （including collagen） degradation, which is possibly related with anti-fibrosis effect of AcSDKP.

关 键 词：矽肺 N-乙酰基-丝氨酰-天冬氨酰-赖氨酰-脯氨酸 基质金属蛋白酶 基质金属蛋白酶组织抑制因子 

分 类 号：R365[医药卫生—病理学] R135.2[医药卫生—基础医学]