尿激酶对急性深静脉血栓形成后血管重构的影响  

Effect of urokinase on vein wall remodeling after deep vein thrombosis in rats

作　　者：杨冰[1] 赵庆华[2] 赵渝[3] 

机构地区：[1]重庆医科大学附属第一医院护理学院,重庆400016 [2]重庆医科大学附属第一医院护理部,重庆400016 [3]重庆医科大学附属第一医院血管外科,重庆400016

出　　处：《第三军医大学学报》2010年第18期1970-1975,共6页Journal of Third Military Medical University

基　　金：重庆市卫生局医学科学技术研究项目(2008-2-60)~~

摘　　要：目的探讨尿激酶对急性深静脉血栓栓后静脉壁胶原增生和基质金属蛋白酶动态表达的影响。方法建立大鼠急性下腔静脉血栓模型,分为尿激酶组、未用药对照组以及假手术组。各组分别于术后第3、5、8、14天获取目标血管段,HE染色光镜观察静脉内膜增生程度;Masson胶原染色计算机图像分析系统定量检测静脉壁胶原沉积量;半定量RT-PCR检测静脉壁MMP-2、MMP-9mRNA表达。Western blot检测MMP-2、MMP-9蛋白表达水平。结果血栓形成及消融过程中内膜持续增生,8d时尿激酶组增生达到峰值,未用药对照组14d时增生仍呈现高水平状态,较尿激酶组增生程度高(P<0.05);②栓后管壁中胶原总量增多,尿激酶组术后第8天其表达处高峰值但增生程度较未用药对照组低(P<0.01);③尿激酶组MMP-2、MMP-9较未用药对照组基因表达提前(P<0.01):尿激酶组MMP-2基因表达在术后第5天升高,第8天最高,伴MMP-2活性增强,14d仍有活性;MMP-9的表达于术后第3天和第8天分别增强10倍和25倍;未用药对照组MMP-2基因表达在术后第8天升高,第14天最高,伴MMP-2活性增强;MMP-9的表达于术后第3天和第14天分别增强19倍和27倍,活性未见改变。结论尿激酶治疗大鼠急性下腔静脉血栓形成,能使MMP-2、MMP-9基因表达提前并相应减轻内膜增生,减少胶原沉积,其中溶栓早期MMP-9表达增强,而在血栓消融后则由MMP-2起主导作用。Objective To investigate the effect of urokinase on hyperplasia of collagen and dynamic expression of matrix metalloproteinase（MMP）in early vein wall remodeling after deep vein thrombosis（DVT）.Methods A total of 84 male 3-month-old Wistar rats were randomly divided into DVT＋ urokinase treatment group（group A）,DVT group（group B）,and sham-operation group,with 28 animals in each group.DVT model was established by ligating the infrarenal inferior vena cava（IVC）.Urokinase at 2×104 U/kg was injected through tail vein at once per day for 10 d in group A,while the rats in group B and C was given normal saline at the same volume.Vein tissue samples with thrombosis were collected in 3,5,8 and 14 d after surgery.Intimal hyperplasia and collagen deposition was observed by light microscopy with HE and Masson staining respectively and analyzed with color image analysis system.The expressions of MMP-2,-9 mRNA and protein in all groups were detected by RT-PCR and Western blotting respectively.Results During the thrombopoiesis and thrombus ablation,intimal hyperplasia reached the peak value in 8 d in group A,and was in a high level in group B even in 14 d,significantly higher than that of group A（P〈0.05）.Collagen deposition was increased in vein wall after thrombosis,and reached the peak in 8 d in group A,but the amount was significant lower compared with that in group B（P〈0.05）.In group A,MMP-2 and-9 gene were expressed earlier than in B group（P〈0.01）.MMP-2 expression begun to increase in 5 d and then reached the peak value in 8 d with MMP-2 activity was enhanced.MMP-9 expression was increased by 10-fold and 25-fold at days 3 and 8 respectively.In group B,MMP-2 gene expression was elevated at 8 d and reached the peak value at 14 d with its activity was enhanced.MMP-9 expression was increased by 19-fold and 27-fold at days 3 and 14,respectively,but there was no change in its activity.Conclusion Urokinase exerts certain effects on the thrombopoiesis in rat DVT,by increasing early MMP-2 and-

关 键 词：尿纤溶酶原激活物 静脉血栓形成 基质金属蛋白酶2 基质金属蛋白酶9 血管中膜 血管内膜 增生 

分 类 号：R322.123[医药卫生—人体解剖和组织胚胎学] R364.15[医药卫生—基础医学]