Research on The Development of Overactive Bladder after Bladder Outlet Obstruction : Basic Research in Rat Model with Partial Urethral Obstruction

膀胱出口梗阻后膀胱过度活动症发展的研究：部分尿道梗阻大鼠模型的基础研究

• 批准号: 14370500
• 负责人: KAKIZAKI Hidehiro
• 金额: $ 4.42万
• 依托单位: HOKKAIDO UNIVERSITY
• 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-14370500/
• 关键词: Bladder outlet obstruction; Urethral obstruction; Overactive bladder; Detrusor overactivity; Bladder afferents; Glutamate receptor; C-fiber; α1D-receptor; C銭維

Neuroplasticity in afferent pathways, including C-fiber afferents, is believed to be one of the major causes of overactive bladder/detrusor overactivity after bladder outlet obstruction (BOO). We examined if capsaicin sensitive C-fiber bladder afferents are involved in the development of detrusor overactivity after BOO in the rat. It is concluded that capsaicin sensitive C-fiber afferents are not essential to induce detrusor overactivity but they are involved in functional alterations in bladder afferent pathways after BOO in the rat.Glutamate receptors have a pivotal role in the micturition reflex pathway. To determine the role of N-methyl-D-aspartate (NMDA) glutamate receptor in the development of functional bladder changes after BOO, we investigated the effects of repeat injection of MK-801, a noncompetitive NMDA receptor antagonist, on the micturition reflex in conscious obstructed rats. In obstructed MK-801 treated rats, there was a significant increase in bladder capacity and voided volume without changes in voiding efficiency or micturition pressure compared with untreated obstructed rats. The development of detrusor overactivity was not prevented by chronic treatment with IVTK-801. Thus it is concluded that BOO causes NMIDA receptor mediated alterations in bladder afferent pathways in the rat.Detrusor overactivity in obstructed rats was suppressed by intrathecal or intrapelvic arterial injection of α1D-receptor antagonist Therefore it is concluded that spinal as well as peripheral α1D-receptors are involved in the pathophysiology of detrusor overactivity associated with BOO.

包括C纤维传入在内的传入通路的神经可塑性被认为是膀胱出口梗阻（BOO）后膀胱过度活动/逼尿肌过度活动的主要原因之一。我们研究了辣椒素敏感的C纤维膀胱传入是否参与了大鼠BOO后逼尿肌过度活动的发展。可以得出结论，辣椒素敏感的C-纤维传入是不是必不可少的，诱导逼尿肌过度活动，但他们参与的功能改变膀胱传入通路后BOO在大鼠。谷氨酸受体在排尿反射通路中有着举足轻重的作用。为了确定N-甲基-D-天冬氨酸（NMDA）谷氨酸受体在BOO后功能性膀胱变化中的作用，我们研究了重复注射非竞争性NMDA受体拮抗剂MK-801对清醒梗阻大鼠排尿反射的影响。与未给药梗阻大鼠相比，MK-801给药梗阻大鼠的膀胱容量和排尿量显著增加，排尿效率或排尿压力无变化。IVTK-801长期治疗不能预防逼尿肌过度活动的发生。结论：BOO可引起NMIDA受体介导的膀胱传入通路改变。鞘内或盆腔动脉注射α 1D受体拮抗剂可抑制梗阻大鼠逼尿肌过度活动。

项目成果

田中 博, 柿崎 秀宏: "排尿障害とalpha1受容体/ラットBOOモデルに対するalpha1ブロッカーの効果"脳21. 6(2). 62-65 (2003)

Hiroshi Tanaka、Hidehiro Kakizaki：“α1 阻滞剂对泌尿功能障碍和 α1 受体/大鼠 BOO 模型的影响”Brain 21. 6(2) (2003)。

Machino R, Kakizaki H, et al.: "Detrusor instability with equivocal obstruction : A predictor of unfavorable symptomatic outcomes after transurethral prostatectomy"Neurourology and Urodynamics. 21. 444-449 (2002)

Machino R、Kakizaki H 等人：“逼尿肌不稳定伴可疑梗阻：经尿道前列腺切除术后不良症状结果的预测因素”神经泌尿学和尿动力学。

Tanaka H, Kakizaki H, et al.: "Effect of preemtive treatment of capsaicin or resiniferatoxin on the development of pre-micturition contractions after partial urethral obstruction in the rat."Journal of Urology. 170. 1022-1026 (2003)

Tanaka H、Kakizaki H 等人：“辣椒素或树脂毒素的预防性治疗对大鼠部分尿道梗阻后排尿前收缩发展的影响。”泌尿学杂志。

Maclino R., Kakizaki H, et al.: "Detrusor instability with equivocal obstruction : A predictor of unfavorable symptomatic outcomes after transurethral prostatectomy"Neurourology and Urodynamics. 21. 444-449 (2002)

Maclino R.、Kakizaki H 等人：“逼尿肌不稳定伴可疑梗阻：经尿道前列腺切除术后不良症状结果的预测因素”神经泌尿学和尿动力学。

Tanaka H, Kakizaki H, et al.: "Effects of chronic blockade of N-methyl-D-aspartate receptors by MK-801 on neuroplasticity of the micturition reflex pathway after partial urethral obstruction in the rat."Journal of Urology. 170. 1427-1431 (2003)

Tanaka H、Kakizaki H 等人：“MK-801 慢性阻断 N-甲基-D-天冬氨酸受体对大鼠部分尿道梗阻后排尿反射通路神经可塑性的影响。”泌尿学杂志。