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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 To investigate the renal protective mechanism of Rofecoxib on renal interstitial fibrosis in rats. Methods Rat models of renal interstitial fibrosis were established with UUO and randomly divided into sham operation group, UUO group and Rofecoxib intervention group. The expressions of COX-2, TGF-1 and renal tubular epithelial cell apoptosis were detected at different time points. Results Compared with the sham-operation group, the expression of TGF-β1 and COX-2 in the UUO group increased significantly as time went by, and more apoptotic cells were detected (P <0.01). Compared with the UUO group, The expression of COX-2 and TGF-β1 were significantly decreased (P <0.01), and the apoptotic cells were significantly decreased (P <0.01). Conclusions Rofecoxib, a specific COX-2 inhibitor, may play a protective role on kidney through blocking the activity of COX-2 in renal tissue, decreasing the protein synthesis of TGF-β1, decreasing excessive apoptosis of renal tubular cells and inhibiting renal allografts.