摘要
目的探讨血管紧张素转化酶抑制剂对肾小球细胞外基质产生和降解的作用。方法用５／６肾切除的方法诱导大鼠肾小球硬化模型并给予血管紧张素转化酶抑制剂苯那普利（６ｍｇｋｇ－１／ｄ）治疗６周，观察了大鼠血压、蛋白尿和残余肾组织的病理改变以及用免疫组化和Ｎｏｒｔｈｅｒｎｚ印迹杂交的方法检测了纤维连接蛋白沉积和血管紧张素Ⅱ１Ａ（ＡＴ１Ａ）受体、纤溶酶原激活物抑制物－１（ＰＡＩ－１）及转化生长因子β（ＴＧＦβ）基因的表达。结果苯那普利治疗能明显降低５／６肾切除大鼠血压、尿蛋白排泄和减轻肾脏的病理改变，并且减少了残余肾组织中纤维连接蛋白的沉积以及降低了ＡＴＩＡ受体、ＰＡＩ－１和ＴＧＦβ基因的表达。结论通过抑制ＰＡＩ－１和ＴＧＦβ基因的表达，苯那普利减少了细胞外基质的产生并促使其降解，这可能是血管紧张素转化酶抑制剂减轻肾小球硬化的重要途径之一。
Objective To study the effect of angiotensin converting enzyme inhibitor(ACEI),benazepril,on the production and degradation of extracellular matrix Methods After the treatment with benazepril(6mg·kg-1/d)for 6weeks, the blood pressure and proteinuria were measured and the renal pathological lesions, the mRNA expressions of angiotensinⅡtype 1A(AT1A)receptor,PAI1 and TGFβ investigated in the 5/6 nephrectomized ratsResults Benazepril not only reduced the blood pressrue,proteinuria and renal pathological injuries,but also significantly decreased the fibronectin deposition and the mRNA expressions of ATIA receptor,PAI1 and TGFβ in the remnant kidney of the 5/6 nephrectomized ratsConclusion The modulation of benazepril on the extracellular matrix metabolism through the PAI1 and TGFβ pathways may be one of the ameliorative mechanism of ACEI on the glomerular sclerosis
出处
《中华肾脏病杂志》
CAS
CSCD
北大核心
1998年第3期139-142,共4页
Chinese Journal of Nephrology
基金
国家自然科学基金优秀中青年人才基金
全军医药卫生"九五"重点项目
