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目的比较他克莫司(FK506)和环孢素A(CsA)所致慢性肾毒性大鼠模型肾组织转化生长因子β1(TGF-β1)及其受体(TβRⅠ和TβRⅡ)的表达。方法分别以FK506和CsA灌胃复制大鼠FK506和CsA慢性肾毒性模型,观察大鼠的一般情况,计算肌酐清除率,观察大鼠肾组织病理变化,以免疫组织化学法检测肾组织中TGF-β1、TβRⅠ、TβRⅡ蛋白表达的变化,原位杂交法检测肾组织中TβRⅠmRNA及TβRⅡmRNA表达的变化。结果CsA组和FK506组的肾小管、小管间质和入球小动脉均有损伤,但CsA组的损伤明显较FK506组重(P<0.05)。正常对照组大鼠肾组织中仅见少量TGF-β1、TβRⅠ和TβRⅡ表达,CsA组和FK506组的TGF-β1、TβRⅠ和TβRⅡ表达均明显增加,但FK506组稍轻;正常对照组大鼠肾组织中仅见少量TβRⅠmRNA、TβRⅡmRNA表达,CsA组和FK506组TβRⅠmRNA、TβRⅡmRNA明显表达,但FK506组较CsA组为轻。结论FK506的慢性肾毒性弱于CsA,它所诱导的大鼠肾组织中TGF-β1及其受体TβRⅠ和TβRⅡ的表达均低于CsA。
Objective To compare the expression of transforming growth factor β1 (TGF-β1) and its receptors (TβRⅠ and TβRⅡ) in renal tissue of chronic nephrotoxic rats induced by FK506 and cyclosporine A (CsA). Methods FK506 and CsA were respectively used to intragastrically instil the FK506 and CsA chronic nephrotoxicity models in rats. The general situation of rats was observed, the creatinine clearance rate was calculated and the pathological changes of renal tissues were observed. The expressions of TGF- β1, TβRⅠ, TβRⅡprotein expression in renal tissue TβRⅠmRNA and TβRⅡmRNA expression changes. Results The renal tubules, tubulointerstitial and afferent arterioles in CsA group and FK506 group were all damaged, but the injury in CsA group was significantly heavier than that in FK506 group (P <0.05). In normal control group, only a small amount of TGF-β1, TβRⅠ and TβRⅡ were expressed in renal tissue, and the expressions of TGF-β1, TβRⅠ and TβRⅡ in CsA group and FK506 group were significantly increased, but slightly in FK506 group. In normal control group, Only a few TβRⅠmRNA and TβRⅡmRNA expression were observed in CsA group and FK506 group, while TβRⅠmRNA and TβRⅡmRNA in FK506 group were significantly higher than those in CsA group. Conclusion The chronic renal toxicity of FK506 is weaker than that of CsA. The expression of TGF-β1, TβRⅠ and TβRⅡ in rat renal tissue induced by FK506 is lower than that of CsA.