尿激酶改善长时间热缺血肾脏功能的实验研究

Urokinase improves renal function of rabbits with long-time warm ischemia

目的探讨尿激酶对长时间热缺血(warm ischemia,WI)肾脏的形态和功能恢复的影响。方法 30只家兔按随机数字表法分为3组:假手术、热缺血组(WI组)、热缺血+尿激酶治疗组(WI+UK组)。夹闭左侧肾动、静脉90 min模拟热缺血过程,HCA液冷灌注及肾脏血流复灌,模拟自体原位肾移植。比较各组血肌酐(Cr)、肾脏组织病理改变(HE、Masson染色)和免疫组化检测血栓调节蛋白(thrombomodulin,TM)。结果与假手术组比较,WI组和WI+UK组术后Cr水平明显升高(P<0.05),术后35 d Cr水平WI+UK组[(118.99±17.18)μmol/L]明显低于WI组[(165.34±8.38)μmol/L,P<0.01]。WI组肾小球内大量微血栓形成,肾小管水肿、坏死;WI+UK组肾小球未见血栓,肾小管未见异常。WI组TM表达明显高于假手术组(P<0.01),WI+UK组明显低于WI组(P<0.05)。结论热缺血90 min后有明显的微血栓形成,导致肾脏结构破坏及肾功能下降。尿激酶治疗后微血栓溶解,有利于肾脏结构和功能恢复。

Objective To explore the impact of urokinase（ UK） on improving the renal function of rabbits with long-time warm ischemia（ WI）. Methods Thirty rabbits were randomly divided into 3 groups：sham operation（ SO） group,WI group,and WI ＋ UK group. WI rabbit model was established by clipping both left renal artery and left renal vein for 90 min. Renal in situ autografting model was simulated by HCA liquid cold perfusion and then blood reperfusion. Serum creatinine（ Cr） was examined in each group.Pathological sections were observed by HE staining and Masson staining. Thrombomodulin（ TM） expression was analyzed by immunohistochemistry（ IHC）. Results On the 35 th day after the operation,the Cr level was greatly increased in the WI group and the WI ＋ UK group than the SO group（ P 〈 0. 05）,while the Cr level（ 118. 99 ± 17. 18 μmol / L） of the WI ＋ UK group was significantly lower than（ 165. 34 ± 8. 38 μmol / L）of the WI group（ P 〈 0. 01）. In the WI group,a large amount of micro-thrombi appeared in the glomeruli,and very severe edema and necrosis were found in the kidney tubules,but in the WI ＋ UK group,there was no abnormality in the glomeruli and kidney tubules. The TM expression of the WI group was greatly higher than that of the SO group（ P 〈 0. 05）,and the TM expression of the WI ＋ UK group was significantly lower than that of the WI group（ P 〈 0. 05）. Conclusion Obvious micro-thrombi are observed after 90-min WI,which leads to destroy of kidney structure and decrease of kidney function. After treatment with UK,the microthrombi are dissolved,and the kidney structure and function are recovered.