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

我们探讨逼尿肌毒蕈碱受体和嘌呤能受体表达的变化是否在膀胱出口梗阻致逼尿肌不稳定（DI）的发病机制中起作用。首先，建立大鼠部分尿道梗阻继发性尿路损伤模型。将硫酸阿托品作为非选择性毒毒碱受体阻滞剂和吡啶多磷酸-6-偶氮苯基- 2 - 4-二磺酸四钠盐（PPADS）作为P2X受体生物抑制剂注入髂总动脉。为了估计逼尿肌收缩力，在聚氨酯麻醉下测量等容量节律性收缩时的最大逼尿肌收缩压力（MCP）。梗阻4周后，MCP和膀胱容量分别提高到对照组的130%和180%。阿托品将MCP抑制至50%，阻断组抑制至70%。阿托品后给药PPADS未改变对照组的MCP，但使阻塞组的MCP降低至阿托品前水平的30%。这些结果表明，在完整排尿反射中，嘌呤能通过P2X受体传递不影响膀胱收缩，而在梗阻膀胱中，嘌呤能收缩约占膀胱收缩强度的40%。前列腺肥大患者逼尿肌通过表达P2X受体增强尿道收缩力。嘌呤能受体拮抗剂可应用于继发性逼尿肌不稳定伴前列腺肥大的治疗。

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.