7/8肾切除大鼠凝血纤溶系统的变化及干预治疗的影响

目的：探讨肾小球硬化及小管间质纤维化过程中肾组织纤溶酶原激活物（PA）和PA抑制物（PAI）－1蛋白表达及干预治疗的影响。方法：7／8肾切除肾功能衰竭大鼠为实验动物模型，随机分为未治疗组和治疗组，观察12周后各组大鼠血尿各项生化指标、尿PA活性及残肾组织常规病理和用免疫组织化学染色定性定量评价残肾组织型PA（tPA)、尿激酶型（uPA)、PAI－1蛋白表达。结果：未治疗组大鼠肾功能进行性丧失，尿PA活性下降，肾组织PAI－1表达增高，而tPA、uPA表达下降，残肾组织出现肾小球硬化和间质纤维化。治疗组大鼠残肾组织tPA、uPA蛋白表达增加，PAI－1表达下降。尿PA活性增加，肾功能改善。结论：水蛭治疗组、苯那普利治疗组及联合治疗组都可以通过改善7／8肾切除大鼠PA／PAI－1系统的紊乱而延缓肾小球硬化和间质纤维化病变的进展。

Change of PAs/PAI-1 system and effect of interfering therapy in 7/8 nephrectomized rats

Objective To investigate the effect of interfering therapy on the protein expression of tissue-type plasminogen activator(tPA), urokinas-type plasminogen activator(uPA) and 1 type plasminogen activator inhibitor(PAI-1) in renal tissue of 7/8 nephrectomized rats. Methods The 7/8 nephrectomized rats were served as experimental animal model. The renal pathological lesions by PAS staining, the protein expression of tPA, uPA and PAI-1 by immunohistochemical staining and the changes of serum/urine biochemical parameters of rats in different treated and untreated groups for 12 weeks were observed. Results In untreated group, the renal function was lost progressively and urinary PA activity decreased; the protein expression of tPA and uPA was down-regulated and PAI-1 was up-regulated in remnant renal tissue; the glomerulosclerosis and tubulointerstitial fibrotic lesions occurred gradually. In each treated group, the renal failure was ameliorated, the urinary PA activity increased, and the protein expression of PAs increased and PAI-1 decreased simultaneously(P <0. 01). Conclusion Hirudo combined with benazepril can delay fibrosis of remnant kidney through the mechanism of modulating or improving the disorders of PAs/PAI-1 system.