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目的探讨环氧合酶-2在单侧输尿管梗阻(UUO)大鼠模型的表达及选择性环氧合酶-2(COX-2)抑制剂塞来昔布对UUO大鼠结缔组织生长因子表达的影响。方法将UUO大鼠随机分为:C:模型对照组,B:布洛芬组,R:塞来昔布组,S:假手术组。B组给予布洛芬300mg·Kg-1·d-1,R组给予塞来昔布10mg·Kg-1·d-1,C组、S组每日给予等体积的生理盐水于造模前一天至造模后14d灌胃,分别于UUO后3、6、14d分批处死,逆转录聚合酶链式反应(RT-PCR)检测COX-1、COX-2、TGF-β1、CTGF的mRNA表达,免疫组化技术检测TGF-β1、CTGF、α-SMA的蛋白水平,放免法检测组织内cAMP的水平。结果与S组相比,UUO后C组COX-2、TGF-β1、CTGF的基因表达显著上调,cAMP的水平下降(UUO3dP<0.05,UUO6d、14dP<0.001)。布洛芬对梗阻肾TGF-β1、CTGF表达及组织内cAMP水平均无显著影响,塞来昔布对梗阻肾TGF-β1的表达无显著改变,但能升高组织内cAMP水平,抑制CTGF的表达,纤维化程度减轻。结论COX-2的产物是导致肾小管间质损伤的重要原因,选择性COX2抑制剂可能部分通过升高组织内cAMP的水平来抑制TGF-β1的下游因子CTGF的表达延缓肾间质纤维化。
Objective To investigate the expression of cyclooxygenase-2 in unilateral ureteral obstruction (UUO) rat model and the effect of selective cyclooxygenase-2 (COX-2) inhibitor celecoxib on the expression of connective tissue growth factor Impact. Methods UUO rats were randomly divided into: C: model control group, B: ibuprofen group, R: celecoxib group, S: sham operation group. Group B was given ibuprofen 300mg · Kg-1 · d-1, Group C was given celecoxib 10mg · Kg-1 · d-1, Group C, Group S were given an equal volume of saline daily before modeling The rats were sacrificed on day 3, 6 and 14 after UUO, and the mRNA expression of COX-1, COX-2, TGF-β1 and CTGF were detected by reverse transcription polymerase chain reaction (RT-PCR) The protein levels of TGF-β1, CTGF and α-SMA were detected by immunohistochemistry and the levels of cAMP in the tissues were detected by radioimmunoassay. Results Compared with group S, the gene expression of COX-2, TGF-β1 and CTGF in UUO group C was significantly increased and the level of cAMP was decreased (UUO3dP <0.05, UUO6d, 14dP <0.001). Ibuprofen had no significant effect on the expression of TGF-β1, CTGF and the level of cAMP in the obstructed kidneys. Celecoxib did not change the expression of TGF-β1 in the obstructed kidneys, but increased cAMP level and CTGF Expression, reduce the degree of fibrosis. Conclusions The products of COX-2 are the main causes of tubulointerstitial injury. Selective COX2 inhibitors may delay renal interstitial fibrosis by inhibiting the expression of cTGF, a downstream factor of TGF-β1, partly by increasing cAMP level in tissues.