选择性环氧化酶-2抑制剂对梗阻性肾病大鼠肾组织中巨噬细胞趋化蛋白-1的调节

Effect of Celecoxib on activation of renal monocyte chemoattractant protein-1 in obstructive nephropathy

目的探讨塞来昔布(celecoxib)与吲哚美辛(indomethacin)比较对单侧输尿管梗阻(UUO)大鼠模型肾脏的保护作用及可能机制。方法大鼠随机分为4组:模型组(UUO组),塞来昔布治疗组(UUO+celecoxib组),吲哚美辛治疗组(UUO+indomethacin组)和假手术组即对照组(SOR)。4周后检测各组大鼠血清肌酐及尿素氮水平,并采用放射免疫方法测定大鼠尿液血栓烷素B2(TXB2)浓度。应用免疫组织化学方法检测肾脏巨噬细胞趋化蛋白-1(MCP-1)、转化生长因子-β1(TGF-β1)及Ⅳ型胶原(ColⅣ)的蛋白水平。结果塞来昔布及吲哚美辛均可以降低尿TXB2浓度,以塞来昔布组更为显著;与对照组相比,其余3组MCP-1、TGF-β1及ColⅣ的蛋白表达水平均显著上升,肾间质纤维化严重;塞来昔布治疗后,上述蛋白表达水平显著下调,肾间质纤维化程度明显减轻。结论塞来昔布能减轻UUO大鼠肾间质纤维化,下调MCP-1的表达,减少肾间质单核巨噬细胞浸润可能是其机制之一。

[Objective] To investigate the protective effect of Celecoxib and its mechanism on renal interstitial fibrosis following unilateral ureteral obstruction （UUO） in rat kidney. [Methods] Rats were randomly assigned to UUO group, Celecoxib treated group, Indomethacin treated group and sham-operation group. At the 4th weekend, the 24-hour urine of the rats were collected from each group and the thromboxane 132 concentration was determined by radioimmunoassay. The protein expression of MCP-1, TGF-β1 and CollV were detected by immunohistochemistry. [Results] Both Celecoxib and Indomethacin reduced the thromboxane B2 concentration , while the effect of eelecoxib was greater. Compared to sham-operation group, the level of MCP-1, TGF-β1 and ColⅣ were significantly increased in other three groups. Whereas Celecoxib markedly suppressed the expression of above-mentioned and improved renal fibrosis. [Conclusion] In short, Celecoxib can ameliorate the renal interstitial fibrosis in UUO rats. The likely mechanisms include down-regulating the expression of MCP-1 and decreasing renal maerophage infiltration.