阻断肾素-血管紧张素对肾病大鼠肾小球硬化ET-1及NO的作用

目的　探讨肾小球硬化与肾组织内皮素 -1(ET -1)和一氧化氮 (NO)的关系 ,以及阻断肾素 -血管紧张素 (RAS)对肾小球硬化的影响。方法　 3 0只SD大鼠单侧肾切除加阿霉素 ( 6mg/kg)尾静脉注射制作肾小球硬化大鼠模型 ,随机分成肾小球硬化组 (D组 ) ,肾小球硬化苯那普利治疗组 (DB组 )和肾小球硬化芦沙坦治疗组 (DL组 ) ,每组各 10只 ,另 10只为假手术组 (C组 )。治疗6周后应用逆转录聚合酶链反应在基因水平检测肾皮质ET -1和诱导型一氧化氮合酶 (iNOS)mRNA表达 ,Western蛋白质印迹测ET-1和iNOS蛋白 ,免疫组织化学方法测定肾组织纤维连接蛋白 (Fn)含量。结果　D组出现明显蛋白尿 ,低蛋白血症及高胆固醇血症 ,与C组比较差异有显著性 ( P <0 0 5 )。肾皮质ET -1mRNA和蛋白比对照组分别上升 2 5 8倍和 1 83倍 ,iNOSmRNA和蛋白上升3 2 8倍和 2 15倍 ,肾皮质Fn也明显上调。应用苯那普利及芦沙坦治疗 6周后 ,血、尿生化改变明显改善 ,病理改变减轻 ,ET -1、iN OSmRNA和蛋白表达及Fn水平降低 ,多组间方差分析差异有显著性意义 (P <0 0 5 )。结论　肾组织ET -1和NO在肾小球硬化早期起重要作用 ,通过苯那普利和芦沙坦阻断RAS ,能减轻肾小球细胞外基质的沉积 ,与ET -1及NO的变化密切相关

The Effect of Rennin-angiotensin System on Endothelin-1 and Nitric Oxide in Rat Glomerulosclerosis

Objective To investigate the correlation among glomerulosclerosis and endothelin-1(ET-1) and nitric oxide(NO), and the effect of blocking renin-angiotensin system(RAS) on rat glomerulosclerosis. Methods 30 SD rats underwent unilateral nephrectomy plus adriamycin (6mg/kg) injection through caudal vein to establish rat glomerulosclerosis models. These rats were divided randomly into glomerulosclerosis group (group D), Benazepril treatment group (group DB) and Losartan treatment group (group DL). Another 10 SD rats served as sham-operation group (group C). 6 weeks after treamtent, the mRNA and protein expressions of ET-1 and iNOS in renal cortex were detected using RT-PCR and Western blotting analysis respectively, and the content of fibronectin(Fn) was measured using immunohistochemical method. Results Group D occurred massive proteinuria, hypoalbuminemia and hypercholesterolemia, which had significant differences compared with group C (P<0 05). Compared with group C, the expression level of ET-1mRNA and protein in the renal cortex of group D increased 2 58 and 1 83 times respectively, the expression level of iNOS mRNA and protein increased 3 28 and 2 15 times respectively, and there was a significant increase in the content of Fn as well. 6 weeks after treatment, there was significant improvement in the blood and urine biochemical indices and renal pathological lesions in groups DB and DL, the mRNA and protein expressions of ET-1 and iNOS were down-regulated, and the expression of Fn protein also decreased(P<0 05). Conclusion ET-1 and NO played important roles in the early stage of rat glomerulosclerosis. Blocking RAS using Benazepril or Losartan could decrease the glomerular extracellular matrix deposit.