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

脑桥排尿中枢尿失禁特异性基因的功能分析

• 批准号: 14370507
• 负责人: YOKOYAMA Osamu
• 金额: $ 8.19万
• 依托单位: Faculty of Medical Sciences, University of Fukui
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14370507/
• 关键词: Cerebrovascular accident; voiding dysfunction; neurogenic bladder; urinary incontinence; neuronal plasticity; prostaglandin; COX-2; EP-1

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

目的：脑梗塞引起的膀胱过度活动症（BO）的发生被认为需要在脑桥排尿中心（PMC）进行转录。我们之前报道过环氧合酶-2（COX-2）mRNA的表达是由PMC中的NMDA（N-甲基-D-天冬氨酸）受体的活性介导的，并且是BO的发生所必需的。本研究旨在检查是否表达 前列腺素（PG）E或D合酶、COX-2下游基因以及PGE2和D水平与左大脑中动脉（MCA）闭塞引起的BO相关。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：采用封堵雌性SD大鼠左侧大脑中动脉的方法诱导脑梗死(CI)。对清醒的大鼠进行膀胱测压检查。样本是在 MCA 闭塞或假手术 (SO) 后 0.25、1、3、5、12 和 24 小时从脑桥背被盖 (DPi) 获得。研究了 MK-801（0.1 mg/kg，静脉注射）这种 NMDA 受体拮抗剂对 MCA 闭塞后 PGES 或 PGDS 表达的影响。实时定量PCR检测DPT中PGES和PGDS的表达。静脉或脑室内给予NS -398或ONO-8711。结果：MCA闭塞后1-24小时，CI大鼠膀胱容量明显减少。MCA闭塞后1小时，与SO大鼠相比，PGES和PGDS mRNA表达显着增加。 MCA 闭塞后至少 12 小时，PGES 和 PGDS 表达始终高于 SO 大鼠。MK-801 预处理抑制膀胱过度活动的发展，并显着降低 DPT 中 PGES mRNA 的表达。MK-801 预处理不影响 PGDS mRNA 的表达。MCA 闭塞后 3 至 5 小时，DPT 中 PGE2 水平升高。 NS-398和ONO-8711抑制脑梗塞引起的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。较少的

项目成果

Niikura S, Yokoyama O, Komatsu K, et al.: "Acausative factor of copulatory disorder in rats following social stress"The Journal of Urology. 168. 843-849 (2002)

Niikura S、Yokoyama O、Komatsu K 等人：“社交压力后大鼠交配障碍的致病因素”泌尿学杂志。

Yokoyama O, Yotsuyanagi S, Akino H, Moriyama N, Matsuta Y, Namiki M: "RNA synthesis in the pons necessary for maintenance of bladder overactivity following cerebral infarction in the rat."J Urol. 169. 1878-1884 (2003)

Yokoyama O、Yotsuyanagi S、Akino H、Moriyama N、Matsuta Y、Namiki M：“脑桥中的 RNA 合成对于维持大鼠脑梗塞后膀胱过度活动是必需的。”J Urol。

Yokoyama O, Komatsu K, et al.: "Overactive bladder-experimental aspects"Scand J Urol Nephrol. Supple 36. 59-64 (2002)

Yokoyama O、Komatsu K 等人：“膀胱过度​​活动症实验方面”Scand J Urol Nephrol。

Nakamura Y, Kontani H, Tanaka T, Yomatsu K, Namiki M, Yokoyama O: "Effects of ATP-dependent potassium channel opener on bladder overactivity in rats with cerebral infarction."J Urol. 168. 2275-2279 (2002)

Nakamura Y、Kontani H、Tanaka T、Yomatsu K、Namiki M、Yokoyama O：“ATP 依赖性钾通道开放剂对脑梗塞大鼠膀胱过度活动的影响。”J Urol。

Niikura S, Yokoyama 0, Komatsu K, Yotsuyanagi S, Mizuno T, Namiki M: "A causative factor of copulatory disorder in rats following social stress."J Urol. 168. 843-849 (2002)

Niikura S、Yokoyama 0、Komatsu K、Yotsuyanagi S、Mizuno T、Namiki M：“社交压力后大鼠交配障碍的致病因素。”J Urol。