氨体舒通对环孢素A致大鼠慢性肾毒性的改善作用

Protective effects of spironolactone on chronic cyclosporine A nephrotoxicity in rats

目的:探讨氨体舒通对大鼠慢性环孢素A(CsA)肾病(CCN)的改善作用。方法:36只雄性SD大鼠在低盐饮食基础上随机分对照组、模型组、治疗组。模型组及治疗组皮下给予CsA15mg/(kg·d),治疗组同时给予氨体舒通20mg/(kg·d)灌胃。第14天和第28天每组随机处死6只大鼠,处死前入代谢笼收集24h尿,测尿肌酐及血肌酐(Scr),计算肌酐清除率(Ccr)。放免法测血浆醛固酮水平。肾脏组织标本行HE和Masson染色,检测肾组织单个核细胞浸润、肾间质纤维化及转化生长因子-β1(TGF-β1)的表达情况。结果:与对照组大鼠相比,实验第2周开始至第4周末,模型组大鼠Ccr降低,单个核细胞计数、TGF-β1明显升高,模型组大鼠血醛固酮、间质纤维化积分在第4周末明显升高;给予氨体舒通治疗后,各项指标在不同时间点均向正常方向发展。结论:醛固酮在CCN的结构和功能变化中起了重要的致纤维化作用,氨体舒通通过抑制肾组织中TGF-β1表达和肾小管间质炎症细胞的浸润,对CCN起到改善作用。

Aim： To evaluate the protective effects of spironolactone on chronic CsA nephrotoxicity（CCN）. Methods： Thirty-six adult male SD rats were allocated into control group, model group, spironolactone group at random. With lowersalt diet, model group and spironolactone group was given CsA at 15 mg/（ kg · d） , meanwhile, spironolactone was given to rats in spironolactone group. At the end of 2 and 4 weeks, 6 rats of each group were sacrificed. Serum and urine creatinine were determined. Creatinine clearance rate（Ccr） was calculated. The level of blood aldosterone was determined by radioimmunoassay. HE and Masson staining was performed. TGF-β1 was determined by immunohistochemical method. Results： The level of blood aldosterone was increased（P 〈 0.05）. Compared with control group, the level of Ccr decreased, the infiltrated mononuclear cells in the interstitial, the degree of tubulointerstitial fibrosis and the level of TGF-β1 and aldosterone increased （P 〈 0.05）. These lesions were significantly ameliorated by spironolactone （ P 〈 0.05 ）. CoNclusioN ： Aldosterone plays an important role in structural and function changes during CCN. Spironolactone could improve those lesions during CCN by reducing the overexpression of TGF-β1 and infiltration of mononuclear cells in the interstitial.