苯那普利对肾病幼鼠纤溶蛋白肾组织定位表达的影响

Effects of lotensin on protein expression of major fibrinolytic components in renal tissues of nephrotic juvenile rats

目的 探讨肾病幼年大鼠肾小球硬化及肾间质纤维化病变进展过程中 ,肾组织尿激酶型纤溶酶原激活物 (u PA )、组织型纤溶酶原激活物 (t PA)及其特异性抑制物 (PAI- 1)蛋白定位表达的特点 ,及予血管紧张素转换酶抑制剂 (ACEI)——苯那普利 (benazepril;lotensin)治疗的影响。方法 采用阿霉素诱导的肾病大鼠为动物模型 ,予 ACEI治疗 12周后测大鼠体重、血压、尿蛋白、及血生化各项指标的变化 ,同时用免疫组织化学染色等方法检测各组肾组织 u PA、t PA和 PAI- 1的蛋白表达的变化特点。结果 肾病大鼠肾组织 PAI- 1表达均高于正常对照组 ,而 u PA、t PA均低于正常组 ;经治疗后肾组织 PA I- 1趋于下降 ,而 u PA、t PA表达趋于增高 (P<0 .0 1)。结论 纤溶系统的平衡紊乱是肾病大鼠肾小球硬化和肾间质纤维化进展中的重要病生理变化之一 ,ACEI治疗可改善 PAs/ PAI- 1的异常表达 ,防止细胞外基质的异常沉积 ,阻止肾小球硬化和间质纤维化病变进展。

Objective To investigate the located protein expression of urokinase type plasminogen activator (uPA),tissue type plasminogen activator (tPA) and 1 type plasminogen activator inhibitor (PAI 1) in renal tissues of nephrotic juvenile rats and the effects of angiotensin converting enzyme inhibitor (ACEI)--lotensin treatment.Methods Adriamycin induced nephritic rats were used as experimental subjects.Twelve weeks after the ACEI treatment,the blood pressure,weight,proteinuria and serum biochemical parameters were detected,respectively.The protein expression of uPA,tPA and PAI 1 was estimated by immunochemical staining in various groups.Results Protein expression of PAI 1 in untreated group increased,but uPA and tPA decreased significantly more than control group.In contrast,PAI 1 decreased but uPA,tPA increased markedly after being treated with ACEI (P<0 01).Conclusion The unbalance of fibrinolytic system may be a critical pathophysiologic changes during glomerulosclerosis and tubulointerstitial fibrosis.ACEI treatment may improve the disorder of PAs/PAI 1 system and decrease abnormal accumulation of extracellular matrix (ECM) induced by PAI 1 overexpression in renal tissues.