目的　探讨肾素 血管紧张素系统 (RAS)在肾病综合征的慢性病理进程中的作用和洛沙坦对肾素 血管紧张素系统 (RAS)的长期阻断效应 ,阐明肾病慢性病理进展的部分机制。方法　 72只SD大鼠随机分为 3组 :(1)正常对照组 ;(2 )肾病组 ;(3)治疗组。分 2次 (间隔 2 0d)自其尾静脉注射阿霉素 (每次 2mg/kg)构建肾病慢性病理进展模型。第 1次注药后 1周 ,予以治疗组大鼠洛沙坦 10mg/(kg·d)灌胃 ,动物实验时间 2 7周。 7周后每 4周每组杀鼠 4只观察大鼠尿蛋白、血清肌酐、肾脏重量 /体重比值、肾脏病理 ,免疫组化法检测肾组织转化生长因子 β1(TGF β1)和胶原蛋白Ⅳ (CollagenⅣ )的蛋白质表达水平 ,逆转录多聚酶链反应 (RT PCR)检测肾组织TGF β1和血管紧张素原 (Ang)的mRNA表达水平。结果　 (1)整个实验期间 ,大鼠 2 4h尿蛋白量、血清肌酐及肾重 /体重比值 ,均是肾病组 >治疗组 >对照组 (P <0 0 1) ;(2 ) 2 7周末 ,肾小球硬化分数 :对照组为 2 9± 5 ,肾病组为 2 6 1± 39,治疗组为 10 9± 12 ;小管间质病理损害分数 :对照组为 1 8± 0 5 ,肾病组为 13 0± 1 4 ,治疗组为 8 5± 1 3。(3) 11周末后 ,大鼠肾组织TGF β1、CollagenⅣ的免疫组化染色阳性细胞计数百分率 ,均以肾病组 >治疗组 >对照组 (P <0 0 1)。 Objective To investigate the role of the renin-angiotensin system (RAS) in chronic pathological progression of nephrotic syndrome and the long-term blocking effect of losartan on the renin-angiotensin system (RAS) and to elucidate some of the mechanisms of chronic pathological progression of nephropathy . Methods 72 SD rats were randomly divided into three groups: (1) normal control group; (2) nephropathy group; (3) treatment group. Divided 2 times (interval 20d) from its tail vein injection of doxorubicin (2mg / kg each time) to build a chronic kidney disease progression model. One week after the first injection, losartan 10 mg / (kg · d) was given intragastrically in the treatment group, and the experimental period was 27 weeks. After 4 weeks of every 7 weeks, 4 rats in each group were observed for urinary protein, serum creatinine, kidney weight / body weight ratio, renal pathology and immunohistochemistry to detect the expression of transforming growth factor β1 (TGFβ1) and collagen Ⅳ CollagenⅣ) protein expression levels, reverse transcription polymerase chain reaction (RT PCR) detection of renal TGFβ1 and angiotensinogen (Ang) mRNA expression levels. Results (1) Urine protein, serum creatinine and kidney weight / body weight ratio of rats in 24 hours were all higher than those in control group (P <0.01); (2) Glomerulosclerosis score was 29 ± 5 in the control group, 26 ± 39 in the nephropathy group, and 10 ± 9 ± 12 in the treatment group. The pathological damage score of the tubulointerstitium was 18 ± 05 in the control group, 13 0 ± 1 4, the treatment group was 85 ± 1 3. (3) After 11 weeks, the percentage of positive cells of TGFβ1 and Collagen Ⅳ in renal tissue of rats were all higher than those of nephrotic group> treated group> control group (P <0.01).