贝那普利联合氯沙坦对环孢素A致大鼠慢性肾毒性的防治作用

Preventive effects of benopril and losartan on cyclosporine A chronic nephrotoxicity in rats

目的:探讨贝那普利和氯沙坦防治环孢素A(CsA)慢性肾毒性的疗效及作用机制。方法:50只SD大鼠随机分为对照组、模型组、贝那普利组、氯沙坦组、联合用药组,每组10只。低盐饲料饲养,以CsA15mg/(kg.d)皮下注射造模,贝那普利组、氯沙坦组、联合用药组分别以单用贝那普利、氯沙坦及两者联用灌胃治疗,对照组和模型组以同体积生理盐水灌胃。于第4周末处死动物,取肾脏作肾组织血管紧张素Ⅱ(AngⅡ)含量测定,Masson染色检测肾脏纤维化,免疫组织化学方法检测生长转化因子-β1(TGF-β1)和胶原Ⅲ(ColⅢ)的表达情况。结果:与对照组相比,模型组的肾组织AngⅡ含量、间质纤维化程度、TGF-β1、ColⅢ明显升高;单药治疗组间质纤维化程度、TGF-β1、ColⅢ较模型组均有所下降,联合用药组低于单药治疗组,差异均有统计学意义(P<0.05)。结论:贝那普利和氯沙坦可能是通过下调TGF-β1,抑制ColⅢ表达,从而延缓CsA大鼠肾间质纤维化进展。两者联合应用,疗效更显著。

Aim ： To investigate the effect of benopril and losartan on CsA chronic nephrotoxicity. Methods：Fifty rats were allocated into control group, model group, benopril group, losartan group and benopril and losartan combination group randomly. With lower-salt diet, model rat was established by CsA （ 15 rag/（ kg · d） ） , meanwhile, normal saline,benopril, losartan,or combination of benopril and losartan was given to rats in these groups. At the end of 4 weeks, kidneys were harvested. Ang Ⅱ was determined by immunoradiometry. Masson staining was performed, as well as TGF-β1 and Col m were determined by immunohistochemistry. Results：The degree of fibrosis, Ang Ⅱ,TGF-β1, and Col m in model group were significantly higher than control group. The degree of fibrosis,TGF-β1, and Col m in benopril group or losartan group decreased compared with model group. The parameters in the combination group were lower than those in benopril group or losartan group（P 〈0.05）. Conclusion：Combination of benopril and losartan attenuate fibrosis in interstitial by down-regulating expression of TGF-β1 and Colin. The effect of combination of benopril and losartan is better than that of benopril or losartan.