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

目的：脑梗死后膀胱过度活动（BO）的发生与桥脑排尿中枢（PMC）的转录有关，我们曾报道过环氧化酶-2（考克斯-2）mRNA的表达是由NMDA活性介导的（N-甲基-D-天冬氨酸）受体的表达，并在BO的发展所必需的。E或D合酶、考克斯-2下游基因、PGE 2和D水平与大脑中动脉（MCA）闭塞所致BO相关。此外，还观察了考克斯-2抑制剂NS-398和EPi受体拮抗剂ONO-8711对BO的影响。方法：采用雌性SD大鼠左侧大脑中动脉（MCA）阻断法建立脑梗死模型。对清醒大鼠进行膀胱测压检查。在MCA阻断或假手术（SO）后0.25、1、3、5、12和24小时从背侧脑桥被盖（DPi）获得标本。 ...更多信息 研究了NMDA受体拮抗剂对MCA闭塞后PGES或PGDS表达的影响。结果：脑梗死大鼠MCA阻断后1-24 h膀胱容量明显减少，MCA阻断后1 h PGES和PGDS mRNA表达较SO大鼠明显增加，但与对照组比较，差异无统计学意义（P > 0. 05）。MK-801预处理可抑制大鼠MCA阻断后12 h的膀胱过度活动，并显著降低DPT中PGES mRNA的表达，但对PGDS mRNA的表达无影响。NS-398和ONO-8711可抑制脑梗死引起的BO的发展。结论：这些结果表明，M、CA闭塞后BO的发生是由NMDA受体活性介导的，并伴有DPT中考克斯-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