Changes in expression of neuroreceptor in unstable bladder and its functional role

不稳定膀胱神经受体表达变化及其功能作用

• 批准号: 12671518
• 负责人: SATO Kazunari
• 金额: $ 2.24万
• 依托单位: Akita University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12671518/
• 关键词: benign prostatic hypertrophy; obstructed bladder; detrusor instability; ATP; P2X raceptor; PPADS; watt factor

We investigated that whether the changes in expression of detrusor muscarinic and purinergic receptors of detrusor play a role in the pathogenic mechanism of detrusor instability (DI) secondary to bladder outlet obstruction. First, a model of secondary DI was established by partial urethral obstruction in rat. Atropine sulfate as a non-selective muscarinic receptor blocker and pyridoxal-phosphate-6-azophenil2 4-disulphonic acid tetrasodium salt (PPADS) as a P2X receptor biocker were administrated into common iliac artery. To estimate detrusor contractility, maximum detrusor contraction pressure (MCP) was measured in isovolumetric rhythmic contraction under urethane anesthesia. MCP and the bladder capacity were increased to 130% and 180% of control in 4 weeks obstructed group, respectively. MCP was inhibited to 50% in control and to 70% in obstructed group by atropine. PPADS administration after atropine did not altered MCP in the control group, but decreased MCP to 30% of pre-atfopine level in the obstructed group. These results suggest that purinergic transmission via P2X receptor does not influence the bladder contraction in intact micturition reflex, on the other hand, purinergic contraction occupies about 40% of bladder contraction strength in obstructed bladder.Detrusor could increase its contractility by expressing P2X receptor for the urethral resistance in benign prostatic hypertrophy. Purinergic receptor antagonist may be applied to the future treatment of secondary detrusor instability with prostatic hypertrophy.

本研究旨在探讨逼尿肌M受体和嘌呤受体表达的变化是否在膀胱出口梗阻后逼尿肌不稳定（DI）的发病机制中发挥作用。首先，采用尿道部分梗阻法建立大鼠继发性DI模型。非选择性毒蕈碱受体阻断剂硫酸阿托品和P2 X受体阻断剂磷酸吡哆醛-6-偶氮苯-2-4-二磺酸四磺酸盐（PPADS）经髂总动脉注入。为了估计逼尿肌收缩力，在尿烷麻醉下测量等容节律性收缩中的最大逼尿肌收缩压（MCP）。梗阻4周组MCP和膀胱容量分别为对照组的130%和180%。对照组MCP抑制率为50%，阻断组MCP抑制率为70%。在对照组中，阿托品后给予PPADS并没有改变MCP，但在阻塞组中将MCP降低至atfopine前水平的30%。结果提示，P2 X受体介导的嘌呤能传递不影响排尿反射时膀胱的收缩，而梗阻性膀胱的嘌呤能收缩约占膀胱收缩强度的40%，逼尿肌可能通过表达P2 X受体而增强其收缩力，从而增加前列腺增生时尿道阻力。嘌呤能受体拮抗剂可能用于治疗继发性逼尿肌不稳定伴前列腺肥大。