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目的 内皮素 1(ET 1)和一氧化氮 (NO)是否参与了肾小球硬化过程尚缺乏广泛的认识。本实验通过制备阿霉素肾小球硬化大鼠模型并应用血管紧张素转换酶抑制剂 (ACEI)莱那普利和血管紧张素Ⅱ Ⅰ型受体拮抗剂芦沙坦干预 ,观察ET 1和NO在肾小球硬化过程中的变化及作用。方法 大鼠随机分成假手术 (对照 )组(C组 ) ,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 ) ,治疗 6周后用RT PCR分别测定肾皮质内皮素 1(ET 1)和诱导型一氧化氮合酶 (iNOS)表达 ,用Westernblotting测定ET 1和iNOS蛋白 ,免疫组化测定肾组织Ⅳ型胶原 (ColⅣ )和纤维连接蛋白 (Fn)。结果 肾小球硬化组出现明显蛋白尿、血白蛋白下降及胆固醇上升和肾小球系膜细胞增生 ,细胞外基质沉积。肾皮质ET 1mRNA和蛋白表达为对照组的 3.5 8倍和 2 .83倍 ,肾皮质iNOSmRNA和蛋白表达为对照组的 4 .2 8倍和 3.15倍 ,肾皮质ColⅣ和Fn表达也明显上调。苯那普利和芦沙坦分别治疗 6周后 ,能明显减轻肾小球硬化的生化改变及病理改变 ,同时下调了ET 1、iNOSmRNA及蛋白表达 ,ColⅣ和Fn水平也降低。结论 ET 1和NO参与了肾小球硬化进展。ET 1andiNOS的抑制阻滞了细胞外基质的沉积 ,从而可以预防肾小球硬化症的发生。
Objective Whether endothelin 1 (ET 1) and nitric oxide (NO) are involved in the process of glomerulosclerosis is not widely recognized. This experiment by adriamycin-induced glomerulosclerosis rat model and the application of angiotensin converting enzyme inhibitor (ACEI) lenacil and angiotensin Ⅱ type I receptor antagonist losartan intervention ET1 and NO In the process of glomerulosclerosis changes and the role. Methods The rats were randomly divided into sham operation group (C group), glomerulosclerosis group (D group), glomerulosclerosis benazepril treatment group (DB group) and glomerulosclerosis losartan treatment group (DL group). After 6 weeks of treatment, the expression of endothelin-1 (ET 1) and inducible nitric oxide synthase (iNOS) in renal cortex were determined by RT-PCR. ET 1 and iNOS protein were detected by Western blotting. Type Ⅳ collagen (Col Ⅳ) and fibronectin (Fn). Results Significant proteinuria, decreased serum albumin and increased cholesterol, mesangial cell proliferation and extracellular matrix deposition were observed in glomerulosclerosis group. The expression of ET 1 mRNA and protein in renal cortex was 3.58 times and 2.83 times that in the control group, and the expression of iNOS mRNA and protein in renal cortex was 4.2 times and 3.15 times that of the control group. The expression of ColⅣ and Fn in renal cortex was also significantly up-regulated. After benazepril and losartan treatment for 6 weeks respectively, the biochemical and pathological changes of glomerulosclerosis were obviously alleviated. At the same time, the expression of ET 1 and iNOS mRNA and protein were decreased, and the levels of Col Ⅳ and Fn were also decreased. Conclusion ET 1 and NO participate in the progression of glomerulosclerosis. Inhibition of ET 1andiNOS blocks the deposition of extracellular matrix, which can prevent the occurrence of glomerulosclerosis.