Rofecoxib对肾间质纤维化大鼠TGF-及肾小管上皮细胞凋亡的影响

摘要

目的 探讨Rofecoxib对肾间质纤维化大鼠的肾脏保护机制.方法 以UUO建立肾间质纤维化大鼠模型,随机分为假手术组、UUO组及Rofecoxib干预组,检测不同时间点肾脏COX-2、TGF- 1及肾小管上皮细胞凋亡的表达.结果 与假手术组相比,UUO组随着模型时间延长,TGF-β1、COX-2蛋白表达明显增加,可检测到较多的凋亡细胞(P<0.01),用药组与UUO组平行相比TGF-β1、COX-2蛋白表达明显减少(P<0.01),凋亡细胞明显减少(P<0.01).结论 特异性COX-2抑制剂Rofecoxib可能通过阻断UUO大鼠肾组织COX-2活性,下调TGF- 的蛋白合成,减少肾小管细胞的过度凋亡,起到肾脏保护的作用.%Objective Observe the effect of seclctive COX-2 inhibitor-Rofecoxib on the renal tubular cell apoptosis,TGF-,COX-2 in rats with UUO.Methods 45 Male SD rats were randomly divide into 3 groups: sham-operated group(A group), UUO group(B group), UUO with rofocoxib treatd group(C group). Kidney were harvest at day 3,7,14 The apoptosis of renal tubular cells was detected by TUNEL.TGF- ,COX-2 were examined by immunohistochemical staining, Histological changes were also observed by HE. Results At every time point, apoptosis cells in renal tubular were significantly increased in the obstructed kidney and reduced by Rofecoxib treatment(P<0.01) The protein level of COX-2,TGF- in B3,B7,B14 groups was various(P<0.01)and significantly higher than that in groupsA3,A7,A14,(P<0.01),but in groups C3,C7,C14 The protein level of COX-2、TGF- was significantly lower than B3,B7,B14 groups(P<0.01).Conclusion Selective COX-2 inhibotor-Rofecoxib reduces COX-2 protein expression, reduce renal cortices TGF-β1 and renal tubular cell apoptosis resulting in decreased tubular damage and interstitial fibrosis.