COX-2 and prostanoid expression in micturition pathways after cyclophosphamide-induced cystitis in the rat
COX-2 and prostanoid expression in micturition pathways after cyclophosphamide-induced cystitis in the rat
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DOI：
10.1152/ajpregu.00465.2002
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发表时间：
2003-02-01
影响因子：
2.8
通讯作者：
Vizzard, MA
中科院分区：
文献类型：
--
作者：
Hu, VY;Malley, S;Vizzard, MA
本研究的目的是确定环氧化酶-2（考克斯-2）及其代谢产物在诱导急性（4 h）、中期（48 h）或慢性（10 d）环磷酰胺（CTX）诱导的膀胱炎后下尿路功能中的作用。从安乐死的雌性大鼠中收获膀胱用于分析。使用清醒膀胱测压法评估考克斯-2特异性抑制剂5，5-二甲基-3-（3-氟苯基）-4-（4-甲磺酰基）苯基2（5 H）-呋喃酮（DFU，5 mg/kg sc）（一种二取代呋喃酮）在CYP诱导的膀胱炎中的作用。急性（12倍）和慢性（9倍）治疗后，炎症膀胱中的考克斯-2 mRNA增加。炎症膀胱组织中考克斯-2蛋白表达高于考克斯-2 mRNA表达。前列腺素D-2-甲肟在膀胱中的表达在急性（3倍）和慢性（5.5倍）膀胱炎中显著增加（P小于或等于0.01）。前列腺素E-2在中度（1.7倍）和慢性（2.6倍）膀胱炎患者中显著（P小于或等于0.01）升高（2倍）。考克斯-2免疫反应细胞分布在整个发炎的膀胱和共表达组胺免疫反应。与经顺铂+溶媒处理的大鼠相比，经顺铂+ DFU处理的大鼠的清醒膀胱测压显示，经顺铂处理后4和48 h排尿间期延长，充盈和排尿期间膀胱内压降低。这些研究表明膀胱考克斯-2及其代谢产物参与CYP诱导的膀胱炎排尿反射改变。
The purpose of this study was to determine the role of cyclooxygenase-2 (COX-2) and its metabolites in lower urinary tract function after induction of acute (4 h), intermediate (48 h), or chronic (10 day) cyclophosphamide (CYP)-induced cystitis. Bladders were harvested from euthanized female rats for analyses. Conscious cystometry was used to assess the effects of a COX-2-specific inhibitor, 5,5-dimethyl-3-(3-fluorophenyl)-4(4-methylsulfonyl) phenyl2( 5H)-furanone (DFU, 5 mg/kg sc), a disubstituted furanone, in CYP-induced cystitis. COX-2 mRNA was increased in inflamed bladders after acute (12-fold) and chronic (9-fold) treatment. COX-2 protein expression in inflamed bladders paralleled COX-2 mRNA expression. Prostaglandin D-2-methoxime expression in the bladder was significantly (P less than or equal to 0.01) increased in acute (3-fold) and chronic (5.5-fold) cystitis. Prostaglandin E-2 was significantly (P less than or equal to 0.01) increased (2-fold) in the bladder with intermediate (1.7-fold) and chronic (2.6-fold) cystitis. COX-2-immunoreactive cell profiles were distributed throughout the inflamed bladder and coexpressed histamine immunoreactivity. Conscious cystometry in rats treated with CYP + DFU showed increased micturition intervals 4 and 48 h after CYP treatment and decreased intravesical pressures during filling and micturition compared with rats treated with CYP + vehicle. These studies suggest an involvement of urinary bladder COX-2 and its metabolites in altered micturition reflexes with CYP-induced cystitis.