Functional analysis of specific genes of urinary incontinence in the pontine micturition center

目的：脑梗死引起的膀胱过度活动（BO）的发展被认为需要脑桥排尿中心（PMC）的转录。我们之前报道过环氧化酶-2(COX-2) mRNA的表达是由PMC中NMDA （n -甲基- d -天冬氨酸）受体的活性介导的，并且是BO发展所必需的。本研究旨在探讨前列腺素（PG） E或D合成酶、COX-2下游基因的表达以及PGE2和D水平是否与左大脑中动脉（MCA）闭塞引起的BO有关。此外，还研究了COX-2抑制剂NS-398和EPi受体拮抗剂ONO-8711对BO的影响。方法：雌性SD大鼠左MCA闭塞致脑梗死（CI）。对清醒的大鼠进行膀胱造影检查。在中动脉闭塞或假手术（SO）后0.25、1、3、5、12和24小时分别从桥背被（DPi）处取标本。研究了NMDA受体拮抗剂MK-801 （0.1 mg/kg, iv）对MCA闭塞后PGES或PGDS表达的影响。实时荧光定量PCR检测PGES和PGDS在DPT中的表达。NS -398或ONO-8711经静脉或脑室内给药。结果：MCA闭塞后1-24小时，CI大鼠膀胱容量明显减少。MCA闭塞1小时后，与SO大鼠相比，PGES和PGDS mRNA表达显著增加。在MCA闭塞后至少12小时，PGES和PGDS的表达始终高于SO大鼠。MK-801预处理可抑制膀胱过度活动的发生，并显著降低DPT中PGES mRNA的表达。MK-801预处理对PGDS mRNA表达无影响。MCA闭塞后3 ~ S小时PGE2水平升高。NS-398和ONO-8711抑制脑梗死所致BO的发展。结论：M， CA闭塞后BO的发生是由NMDA受体活性介导的，并伴有DPT中COX-2和PGES mRNA表达的增加。PG被认为与脑梗死引起的BO密切相关。少

Objectives : Development of bladder overactivity(BO)caused by cerebral infarction is believed to require transcription in the pontine micturition center(PMC).We previously reported that the expression of cyclooxygenase-2(COX-2) mRNA was mediated by the activity of an NMDA (N-methyl-D-aspartate) receptor in the PMC and necessary for the development of BO.This study was undertaken to examine whether the expression of prostaglandin (PG) E or D synthase, downstream gene of COX-2, and levels of PGE2 and D were related to BO induced by left middle cerebral artery (MCA) occlusion. Furthermore, the effects of NS-398, COX-2 inhibitor, and ONO-8711, EPi receptor antagonist, on BO were studied. Methods : Cerebral infarction(CI) was induced by left MCA occlusion in female SD rats. Awake rats were cystometrically examined. Specimens were obtained from the dorsal pontine tegmentum (DPi) 0.25, 1, 3, 5,12, and 24 hours after MCA occlusion or a sham operation (SO).The effects of MK-801 (0.1 mg/kg, iv), … More an NMDA receptor antagonist, on PGES or PGDS expression following MCA occlusion were studied. Expressions of PGES and PGDS in the DPT were monitored with real-time PCR.NS -398 or ONO-8711 was intravenously or intracerebroventriculaly administered.Results : Bladder capacity of CI rats was significantly reduced 1-24 hours after MCA occlusion.One hour after MCA occlusion, PGES and PGDS mRNA expression had significantly increased, as compared to that in SO rats. PGES and PGDS expressions remained consistently higher than those in SO rats at least 12 hours after MCA occlusion.Pretreatment with MK-801 inhibited the development of bladder overactivity and significantly reduced the expression of PGES mRNA in the DPT.The expression of PGDS mRNA was not influenced by pretreatment with MK-801.The level of PGE2 increased 3 to S hours after MCA occlusion at the DPT. NS-398 and ONO-8711 inhibited the development of BO caused by cerebral infarction. Conclusion: These results indicate that the development of BO following M, CA occlusion is mediated by the activity of an NMDA receptor and accompanied by an increase in COX-2 and PGES mRNA expression in the DPT.PG is believed to be closely related to the BO caused by cerebral infarction. Less