安体舒通对大鼠慢性环孢素A肾毒性的保护作用

Protective effects of Spironolactone on chronic cyclosporine A nephrotoxicity in rat models

目的:观察醛固酮拮抗剂——安体舒通对慢性环孢素A(CsA)肾毒性发生及发展的影响。方法:健康雄性SD大鼠,低盐饮食1周后随机分为对照组(n=12)、模型组(CsA皮下注射,n=12)和治疗组(CsA皮下注射+安体舒通灌胃,n=12)。于实验35d时处死大鼠,检测大鼠肌酐清除率(Ccr)、血醛固酮水平,Masson染色观察肾脏病理,免疫组化检测肾组织转化生长因子-β1(TGF-β1)的表达。结果:与对照组相比,模型组大鼠体重明显下降(P<0.01),给予安体舒通后大鼠体重下降减慢(P<0.05);与对照组比较,模型组、治疗组大鼠Ccr均下降(P<0.05),但治疗组较模型组下降缓慢(P<0.05);与对照组比较,模型组、治疗组大鼠血醛固酮水平均明显升高(P<0.05),但治疗组与模型组相比,无显著性差异;与对照组相比,模型组大鼠肾脏出现明显间质纤维化(P<0.05),治疗组较模型组明显减轻(P<0.05);与对照组相比,模型组肾组织TGF-β1表达增强(P<0.05),治疗组较模型组明显减弱(P<0.05)。结论:醛固酮参与慢性CsA肾毒性的发生及发展,安体舒通可抑制慢性CsA肾毒性肾组织中TGF-β1的表达,进而抑制CsA诱导的肾间质纤维化。

objective：To investigate the effect of Spironolactone on chronic cyclosporine A nephrotoxicity in rat models.Methods：Normal male SD rats with low-salt diet were randomly divided into three groups,control group（n=12）,model group（CsA subcutaneous daily injection,n=12）and treatment group（CsA subcutaneous injection and Spironolactone given by gastric gavage,n=12）.At the 35th day of the experiment,creatinine clearance rate（Ccr）and serum aldosterone were determined.Masson staining and immunohistochemistry were performed to observe the morphological changes and TGF-β1 expression.Results：In comparison with control group,the rat body weight of model group was significantly decreased（P〈0.01）,these were significantly ameliorated by Spironolactone（P〈0.05）;the Ccr of model group and treatment group was decreased compared with the control group（P〈0.05）,but that of treatment group decreased slowly than that of model group（P〈0.05）.Blood aldosterone level of model group and treatment group was increased compared with that of control group（P〈0.05）,but that of treatment group showed no significant difference compared with that of model group.The rat kidney of model group occurred obvious tubulointerstitial fibrosis compared with control group（P〈0.05）,and that of treatment group was obviously released than that of model group（P〈0.05）.The TGF-β1 of model group was higher（P〈0.05）and that of treatment group was lower than that of control group（P〈0.05）.Conclusion：Aldosterone plays an important role in producing function and structural changes associated with chronic CsA nephrotoxicity.Spironolactone improves the tubulointerstitial fibrosis induced by CsA through inhibiting the expression of TGF-β1.