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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 the proliferation of collagen wall and the dynamic expression of matrix metalloproteinases after acute deep venous thrombosis. Methods Acute inferior vena cava thrombosis model was established and divided into urokinase group, untreated control group and sham operation group. The target vascular segments were obtained on the 3rd, 5th, 8th and 14th postoperative day in each group, the degree of venous intimal hyperplasia was observed by HE staining, the deposition of collagen was quantified by Masson’s collagen staining computer image analysis system, PCR was used to detect the expression of MMP-2 and MMP-9 mRNA in the vein wall. Western blot detection of MMP-2, MMP-9 protein expression levels. Results Endometrial hyperplasia was observed during thrombosis and ablation, and peaked at 8th day in urokinase group. Hyperplasia was still at a high level on the 14th day in untreated control group, which was higher than that in urokinase group (P <0.05). The total amount of collagen in the wall of the urokinase group was higher than that of the untreated control group (P <0.01). On the 8th day after operation, the expression of MMP-2 and MMP-9 in urokinase group was higher than that of the control group The expression of MMP-2 in urokinase group increased on the fifth day after operation, the highest on the eighth day, the activity of MMP-2 was increased, and the activity of MMP-2 was still on the 14th day. The expression of MMP-9 The expression of MMP-2 in untreated group increased on the 8th day after operation, the highest on the 14th day, with the increase of the activity of MMP-2. The expression of MMP- 9 expression increased 19 times and 27 times respectively on the 3rd and 14th days after operation, but the activity did not change. Conclusion Urokinase treatment of acute vena cava thrombosis in rats can make MMP-2, MMP-9 gene expression in advance and correspondingly reduce intimal hyperplasia, reduce collagen deposition, including early thrombolytic MMP-9 expression increased, and in the thrombus ablation After by the MMP-2 plays a leading role.