Suramin对环孢素A诱导的大鼠肾毒性的影响

Effect of Suramin on Cyclosporine A induced nephrotoxicity in rats

目的探讨Suramin对环孢素A(CsA)所致肾毒性的拮抗作用及其相关机制。方法将40只雄性SD大鼠随机分为对照组、CsA组、CsA+小剂量Suramin组和CsA+大剂量Suramin组,每组10只。分别给药5周后检测4组大鼠24h尿蛋白、尿α1-微球蛋白(MG)、β2-MG和N-乙酰-β-D氨基葡萄糖苷酶(NAG)、血肌酐(SCr)、血尿素氮(BUN)、血尿酸(UA)和胱抑素C(Cys C),并计算内生肌酐清除率(Ccr)。通过Masson三色染色法对大鼠肾脏组织进行染色并计算其肾间质纤维化指数。采用免疫组化法检测4组大鼠转化生长因子(TGF)-β1、胶原(collagen)-Ⅰ和纤维连接蛋白(fibronectin)在肾组织中的表达并计算上述指标的平均光密度值(AOD)。结果CsA组大鼠的尿α1-MG、β2-MG、NAG、BUN、UA和Cys C水平均明显高于对照组,Ccr水平明显低于对照组(P<0.05)。CsA+小剂量Suramin组和CsA+大剂量Suramin组大鼠的尿α1-MG、β2-MG、NAG、BUN、UA和Cys C水平均明显低于CsA组,Ccr水平均明显高于CsA组(P<0.05)。CsA组大鼠肾间质纤维化指数和TGF-β1、collagen-Ⅰ、fibronectin的AOD值均明显高于对照组,CsA+小剂量Suramin组和CsA+大剂量Suramin组大鼠的上述指标均明显低于CsA组(P<0.05)。结论Suramin能拮抗CsA诱导的大鼠肾毒性,TGF-β1表达下调可能参与了Suramin抑制肾间质纤维化的病理生理过程。

Objective To explore the effect of Suramin on Cyclosporine A(CsA)-induced nephrotoxicity in rats and the relevant mechanism.Methods Forty male SD rats were randomly divided into control group,CsA group,CsA+Suramin(low dose)group and CsA+Suramin(high dose)group,with 10 rats in each group.After 5 weeks of administration,24h urine protein,α1-microglobulin(MG),β2-MG,N-acetyl-β-D-glucosaminidase(NAG),serum creatinine(SCr),blood urea nitrogen(BUN),uric acid(UA)and cystatin C(Cys C)in 4 groups were detected.The values of creatinine clearance(Ccr)were calculated.Masson trichrome staining was performed to estimate the degree of interstitial fibrosis.The expression of transform growth factor(TGF)-β1,collagen-Ⅰand fibronectin were determined qualitatively by immunohistochemistry.The corresponding values of average optical density(AOD)of the above indicators were determined.Results The levels ofα1-MG,β2-MG,NAG,BUN,UA and Cys C in CsA group were higher than those in control group,while the level of Ccr was lower than that in control group(P<0.05).The levels ofα1-MG,β2-MG,NAG,BUN,UA and Cys C in CsA+Suramin(low dose)group and CsA+Suramin(high dose)group were lower than that in CsA group,the level of Ccr was higher than that in CsA group(P<0.05).The degree of interstitial fibrosis and the AOD of TGF-β1,collagen-Ⅰ,fibronectin in CsA group were higher than those in control group,while the above indicators in CsA+Suramin(low dose)group and CsA+Suramin(high dose)group were lower than those in CsA group(P<0.05).ConclusionSuramin may probably antagonize the nephrotoxicity induced by CsA.Down regulated expression of TGF-β1 may probably associated with the mechanism of interstitial fibrosis.