尿激酶对人血管内皮细胞mmp-9表达的影响及机制-第三军医大学学报.docVIP

尿激酶对人血管内皮细胞MMP-9表达的影响及机制 张树堂 ，李光勤（重庆医科大学附属第一医院神经内科，重庆医科大学基础医学研究所，重庆　400016） 摘要：目的 探讨尿激酶对人血管内皮细胞MMP-9表达的影响及机制。方法 将正常条件下培养的人脐静脉血管内皮细胞分为5组：第1组为空白对照，第2组加入尿激酶，第3、4、5组在加入尿激酶前分别加入MEK抑制剂PD98059、NF-κB抑制剂PDTC、AP-1抑制剂Curcumin。分别用RT-PCR和激光共聚焦技术检测细胞MMP-9 mRNA和蛋白表达量的变化。结果 第2组MMP-9 mRNA和蛋白表达量较第1组显著升高，其余3组较第2组显著降低。结论 尿激酶上调人血管内皮细胞MMP-9表达，其机制与Ras-Raf-MEK1/2-ERK1/2信号转导途径以及NF-κB和AP-1有关。 关键词：血管内皮细胞；尿激酶；MMP-9 中国图书法分类号：R 文献标志码：A 　　 The effect of urokinase on the expression of MMP-9 in human endothelial cell and its mechanism ZHANG Shu-tang, LI Guang-qin (Department of Neurology，the First Affiliated Hospital of Chongqing Medical University，Chongqing 400016，China) Abstract：Objective To investigate the effect of urokinase on the expression of MMP-9 in human endothelial cell and its mechanism. Methods The human umbilical vein endothelial cell cultured in normal condition were divided into five groups: the first group was blank control, the second group was given urokinase, the third、fourth and fifth group was treated with MEK inhibitor PD98059、NF-κB inhibitor PDTC、AP-1 inhibitor Curcumin respectively before urokinase was added in. The expression of MMP-9 mRNA and protein in all the groups was detected by RT-PCR and Laser-Confocus respectively. Results The mRNA and protein expression of MMP-9 in the second group were increased obviously, compared with the first group. Compared with the second group, the mRNA and protein expression of MMP-9 in the third、fourth and fifth group were decreased significantly. Conclusion Urokinase can upregulate the MMP-9 mRNA and protein expression of human endothelial cell, the mechanism is related to the Ras-Raf-MEK1/2-ERK1/2 signal transduction pathway , also to NF-κB and AP-1. Key Words：Endothelial cell; Urokinase; MMP-9 ——————————————————————— 作者简介：张树堂，男，硕士研究生。电话E-mail：155084611@ 通信作者：李光勤，E-mail： 目前，国际上普遍认可的溶栓药物主要有两种—tPA和尿激酶。其中tPA在国外应用较多，而我国主要的溶栓药物是尿激酶。有关tPA对MMP-9表达的影响及机制已比较明确，但未见尿激酶对MMP-9表达的影响及机制的研究。本研究通过离体人血管内皮细胞培养，观察尿激酶对MMP-9表达