尿激酶联合黄芪对环孢素A诱导的肾病大鼠肾组织Snail1表达的影响及意义

Effect of urokinase and astragalus mongholicus on expression of Snail1 in rats with cyclosporin A induced nephropathy

目的:探讨尿激酶(u-PA)联合黄芪(AM)对环孢菌素A(CsA)诱导的肾病大鼠肾组织Snail1蛋白表达的影响及意义。方法:采用灌胃给以CsA(25mg·kg-1.d-1),复制大鼠慢性肾病模型,将大鼠随机分为5组:对照组、模型组、u-PA、AM及联合治疗组,4周末取标本。Masson染色观察肾间质纤维化;免疫组织化学和Western印迹检测大鼠肾组织Snail1、E-钙黏蛋白(E-cadherin)和成纤维细胞特异蛋白1(FSP1)的表达。结果:与对照组相比,模型组肾组织胶原沉积加重,Snail1蛋白表达显著上调,E-cadherin蛋白表达明显减少,FSP1表达明显增强(均P<0.05)。与模型组相比,治疗各组胶原沉积减弱、Snail1、FSP1表达均被显著抑制(均P<0.05);E-cadherin表达则增高(P<0.05),且联合组的治疗效果更显著。结论:u-PA与AM能减轻CsA诱导的肾脏纤维化,这机制可能与其抑制肾组织Snail1的表达有关。

AIM：To explore the effect of urokinase （u -PA） and astragalus mongholicus（AM） on expression of Snail1 in rats with cyclosporin A （CsA） induced nephropathy. METHODS：Male SD rats were treated with CsA （25 mg·kg-1.d-1 ） by gavage to induce chronic kidney disease. The rats were randomly divided into 5 groups：control group,CsA group,u -PA group,AM group and combination group. Renal interstitial fibrosis was graded according to Masson staining. The expression of Snail1 was examined by immunohistochemistry and Western blotting. The expression of Ecadherin and FSP1 was also determined by Western blotting. RESULTS：The levels of collagen deposition and the expression of Snail1 and FSP1 in CsA group and treatment groups were significantly increased as compared to control group （P 0. 05）,but the expression level in the treatment groups was lower than that in CsA group （P 0. 05）. E-cadherin was decreased in CsA group,while such effects were significantly abrogated in the treatment groups （P 0. 05）. The best therapeutic efficacy was observed in combination group. CONCLUSION：Snail1 plays an important role in processing renal fibrosis through mediating epithelial-mesenchymal transition. Urokinase and astragalus mongholicus attenuate renal fibrosis in rats with cyclosporin A induced nephropathy,the mechanism may be related to the inhibition of Snail1 expression and the subsequent prevention of tubular epithelial-mesenchymal transition.