| Abstract: | 下泌尿道儲尿及排尿的功能是靠膀胱 (bladder)、膀胱頸（bladder neck）、尿道 (urethra)完成。膀胱活動主要由副交感神經系統 （parasympathetic nervous system）調控；膀胱頸由下腹神經 (hypogastric nerve) 控制；而尿道分別由體神經 （somatic nervous system）和自主神經系統 (autonomic nerve system) 所調控。骨盆神經-尿道反射研究，反覆性或強烈刺激骨盆傳入神經，會引發明顯的長期增益效應，對於尿道能產生足夠的阻力，在尿液禁制能力中扮演重要角色。cGMP 與蛋白激G (protein kinase G; PKG) 訊息傳遞路徑，證實和平滑肌放鬆相關。在實驗上，將動物體給予尿胺 (urethane) 麻醉後，給予椎管插管，並將腹腔打開，膀胱頂插管並做外尿道肌電圖 (external urethral sphincter– electromyogram；EUSE) 的紀錄，並且分離出骨盆神經 (pelvic nerve)，以電刺激的方式促使產生骨盆神經-尿道反射 (pelvic-urethra reflex; PUR)。在測試性刺激 (test stimulation; TS) 時，其 EUSE 活動性為：1.22 ± 0.09 spikes/stimulation (P<0.01, n =54) 和反覆性刺激 (repetitive stimulation; RS)，其 EUSE 活動性為：18.07 ± 0.98 spikes/stimulation (P<0.01, n =54)；在反覆電刺激紀錄狀況穩定後，椎管內給予藥物 APV 後，EUSE會被APV所抑制，也就是骨盆尿道反射塑性被抑制，然而實驗中後續再給予的autocamtide 2-related inhibitory peptide (AIP)、Nω-Nitro- L-arginine methyl ester hydrochloride (L-NAME 50 mg/ml),1H- [1, 2, 4] Oxadiazolo [4, 3 - a] quinoxalin (ODQ, in DMSO: 5 mg/mL)皆會抑制EUSE活動力的反應。而椎管內給予L-arginine、protoporphyrin IX and 8-Bromoguanosine 3’, 5’-cyclic monophosphate sodium salt monohydrate (8-bromo-cGMP 100 mg/ml 0.22 mM)，皆會使原本被抑制的EUSE反射活動力回復。根據這些結果，藥物對於骨盆神經-尿道反射塑性 (plasticity) 有顯著的抑制或反抑制的情形，亦也證實骨盆神經-尿道反射塑性和蛋白質激G訊息路徑兩者呈現關聯。
Lower urinary tract function of urine storage and micturition are by bladder, bladder neck, urethra and external urethral sphincter (EUS).The bladder major activity is regulated parasympathetic nervous system. The bladder neck is by hypogastric nerve , furthermore, somatic nervous system and autonomic nerve system modulated the urethra. In recent studies on pelvic-urethral reflex (PUR) activities have shown repetitive/titanic stimulation of thepelvic afferent fibers induced a distinct and long-lasting potentiation in PUR activities and the PUR is essential for the urethra to develop sufficient resistance to maintain urine continence. The cGMP and protein kinase G (PKG) signaling pathway were confirmed that has some effects in certain neural cells, in addition, has demonstrated can mediated smooth muscle relaxation. In experimentally, animals were anesthetized with subcutaneous urethane, intrathecal, and then scissor the abdomen to dissociated and transected the pelvic nerve. Furthermore, it used to recording the external urethral sphincter–electromyogram. Repetitive stimulation (RS, 1 Hz) induced a potentiation in the pelvic nerve to urethra reflex (PUR) activities. This potentiation in pelvic-urethral reflex (PUR)
activity induced by repetitive stimulation was abolished by APV (D-2-amino-5- phosphonoraleric acid, i.t. 100 μM, 2–5 μl), autocamtide 2-related inhibitory peptide (AIP), Nω-Nitro-L-arginine methyl ester hydrochloride (L-NAME 50 mg/ml),1H- [1, 2, 4] Oxadiazolo [4, 3 - a] quinoxalin (in DMSO: 5 mg/mL). Intrathecal L-arginine (50 mg/ml; 20 μl), protoporphyrin IX and 8-Bromoguanosine 3’, 5’-cyclic monophosphate sodium salt monohydrate (8-bromo-cGMP 100 mg/ml 0.22 mM) induced a potentiation of PUR. All these results demonstrated that protein kinase G pathway may be involved glutamatergic NMDA receptor-mediated potentiation in PUR activities. |
