福辛普利对慢性肾功能衰竭幼鼠凝血纤溶变化的干预影响

目的探讨血管紧张素转换酶抑制剂(ACEI)——福辛普利干预治疗对幼年大鼠慢性进展性肾脏病变过程中肾组织组织型纤溶酶原激活物(tPA)、组织型纤溶酶原激活物特异性抑制剂(PAI)-1蛋白表达的影响。方法以5/6肾切除SD大鼠为实验动物模型,予ACEI治疗12周后分别检测大鼠体重、血压、血尿生化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tPA、PAI-1蛋白表达。结果于5/6肾切除后,大鼠肾功能进行性丧失,表现为尿蛋白、血压、血尿素氮(BUN)、肌酐(Scr)及血脂增高,残肾组织出现肾小球硬化和间质纤维化。免疫组织化学染色提示肾组织PAI-1表达增高,而tPA表达下降。经ACEI治疗后,大鼠肾功能改善、血压下降、尿蛋白下降、残肾组织tPA蛋白表达增加、PAI-1表达下降。结论ACEI具有改善5/6肾切除大鼠凝血纤溶系统紊乱的作用。

Effects of fosinopril, an angiotensin converting enzyme inhibitor, on tPA/PAI-1 functions in young rats with chronic renal failure

Objective To investigate the effects of fosinopril,an angiotensin converting enzyme inhibitor(ACEI) on the protein expression of tissue plasminogen activator(tPA) and type-1 plasminogen activator inhibitor(PAI-1) in progressively sclerotic or fibrotic renal tissue of 5/6 nephrectomized rats.Methods The 5/6 nephrectomized SD rats as experimental animal models were treated with ACEI for 12 weeks,and were then sacrificed and collected for blood samples and remnant renal tissues.We evaluated the renal pathological lesions by PAS staining and the protein expression of tPA and PAI-1 by immunohistochemistry.The weight,blood pressure,proteinuria,serum/urine biochemical parameters were measured,respectively.Results After 5/6 nephrectomy,the rats experienced progressive renal failure as noted by proteinuria,hypertension,hyperlipidemia,elevated levels of serum creatinine and BUN,as well as occurrence of glomerulosclerosis and tubulointerstitial fibrosis over time.Immunostaining suggested down-regulated tPA expression and up-regulated PAI-1 expression in remnant renal tissue in untreated group.With ACEI treatment,the renal failure,hypertension and proteinuria ameliorated significantly,and the expressions of tPA and PAI-1 were reversed simultaneously,as compared with untreated group(P<0.01) .Conclusion Fosinopril appeared to interfere with fibrosis process in remnant kidney by modulating or improving the disorders of tPA/PAI-1 system.