塞来昔布上调梗阻肾cAMP水平抑制结缔组织生长因子的表达  

Celecoxib Suppresses the Expression of Connective Tissue Growth Factor by up-regulating cAMP in Rats with Unilateral Ureteral Obstruction Model

作　　者：肖厚勤[1] 张建鄂[1] 丁国华[2] 张永[1] 王晓勋[3] 刘志祥[3] 张庆红[1] 李涛[1] 乐发国[1] 

机构地区：[1]郧阳医学院附属太和医院肾内科,湖北十堰442000 [2]武汉大学人民医院肾内科 [3]湖北省十堰市太和医院生命科学研究所

出　　处：《中国医师杂志》2005年第9期1171-1174,共4页Journal of Chinese Physician

摘　　要：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 regulation of cyclooxygenase-2 expression and mechanism of selective cyclooxygenase-2 inhibitor Celecoxib suppressing tubulointerstitial fibrosis of rats with unilateral ureteral obstruction（UUO） model. Methods The UUO models were induced by ligating the left ureter. Rats were randomly divided into bulofen group （group B）, Celecoxib group （group R）, model group （group C） and sham operation group （group S）. Rats in group B were given bulofen 300mg·Kg^-1·d^-1, and in group R were given Celecoxib 10mg·Kg^-1·d^-1 by gastric garage from 24 h before the obstruction to 14 days after the induction. Rats were sacrificed at 3d, 6d and 14d in batch after the UUO models were induced. The mRNA expressions of cyclooxygenase-1（COX-1）, cyclooxygenase-2（COX-2）, transforming growth factor-beta 1 （TGF-β1）, and connective tissue growth factor （CTGF） were detected by RT-PCR. The protein expressions of TGF-β1, CTGF and α-SMA were detected using immunohistochemistry and the content of cAMP was determined by radioimmuno-assay. Results Compared with group S, the mRNA expressions of COX-2, TGF-β1 and CTGF in group C increased markedly after UUO treatment, and the content of cAMP decreased. It showed no significant difference in the mRNA expressions of TGF-β1, CTGF and the content of cAMP for the Bulofen treatment in the UUO model. With the Celecoxib treatment, there was no significant difference on the mRNA expression of TGF-β1, but the content of cAMP increased and the expression of CTGF decreased. Conclusion The COX-2 plays an important role in lesion of tubulointerstitial. Selective cyclooxygenase-2 inhibitor can partially up-regulate the content of cAMP and down-regulate the expression of CTGF, the downstream factor of TGF-β1, which may postpone the renal interstitial fibrosis.

关 键 词：环氧合酶-2 转化生长因子β1 结缔组织生长因子 塞来昔布 单侧输尿管梗阻 肾小管间质损伤 cAMP P水平 选择性COX2抑制剂 上调 

分 类 号：R692[医药卫生—泌尿科学] R693.2[医药卫生—外科学]