他克莫司和环孢素A对大鼠肾脏转化生长因子及其受体表达影响的比较

Comparison of expression of renal transforming growth factor-β_1 and its receptors in rats treated by(cyclosporine) A and tacrolimus

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 renal transforming growth factor-β1, （TGF-β1, ）, its receptors type I and Ⅱ （TβR I and TβR Ⅱ ） in two rat models of chronic nephropathy induced by CsA and FK506 respectively. Methods Rat models of chronic CsA-/FK506-induced nephropathy were established by administering sandimun Neoral and Prograf separately. Then their kidneys were dissected and the protein expression of TGF-β1, , TβR I and TβR Ⅱ , the mRNA levels of Tβ1R I and Tβ1R Ⅱ was detected by using immunohistochemistry （IHC） and in situ hybridization （ISH） respectively. Results The IHC revealed that the integrated optical densities （IODs） of renal TGF-β1, TβR I and TβR Ⅱ were 605.24 ± 140. 24, 876. 28 ± 208. 73 and 981.59 ± 258. 65 respectively in CsA-treated rats, 488. 37 ±101.76, 586. 63 ± 131.21 and 543. 34 ± 105.26 respectively in FK506treated ones. The ISH indicated that the IODs of renal TβR I and TβR Ⅱ mRNA were 905.08 ± 158. 75 and 1090. 92 ± 242.73 respectively in CsA-treated rats, 661.37 ± 205.65 and 716. 27 ± 195.55 respectively in FK506-treated ones. The difference of the above-mentioned five factors between the two groups was significant （P〈0. 05）. Concision The nephrotoxicity of FK506 was less than that of CsA. The expression of renal TGF-β1, its receptors TβR I and TβR Ⅱ in FK506-treated rats was less than that in CsA-treated ones.