Pang Lei, Shao Jinkai, Wen Xiaodong, Liu Dong, Zhang Zhijia, Shuang Weibing
Department of Graduate, Shanxi Medical University, Taiyuan, China.
Department of Urology, Fifth Affiliated Hospital of Shanxi Medical University, Taiyuan, China.
Transl Androl Urol. 2022 Mar;11(3):304-312. doi: 10.21037/tau-22-23.
The role of purinergic receptor P2X3 in pathological bladder dysfunction and chronic pelvic pain remains unclear. We aim to investigate the effect of P2X3 on bladder function in interstitial cystitis (IC) through the IC rat model induced by cyclophosphamide (CYP).
A total of 120 female Sprague-Dawley (SD) rats were randomly divided into 6 groups: control, CYP-4h, CYP-48h, CYP-10d, CYP-30d, and CYP-45d groups. The control group was injected with normal saline. The rats in the CYP-4h and CYP-48h groups were given a single high dose. The rats in the CYP-10d, CYP-30d, and CYP-45d groups were given a low dose of CYP repeatedly every three days. Bladder voiding function was measured using urodynamic techniques to observe the effect of the P2X3 receptor on bladder function in CYP-induced IC.
The rats in the CYP-4h group showed significant overactivity of the bladder compared with the control group, the bladder voiding interval was shortened (P<0.01), and the maximal voiding pressure was increased (P<0.01). At the same time, the degree of overactive bladder in the CYP-48h, CYP-10d, CYP-30d, and CYP-45d groups became increasingly serious, the interval of bladder micturition was shortened stepwise (P<0.01), and the maximal micturition pressure was increased stepwise (P<0.01). Compared with the control group, the CYP-48h group mainly showed a shorter bladder voiding interval (P<0.01), lower voiding volume, and higher activation of mast cells and inflammatory factors in the bladder. In the CYP-10d group, bladder mast cell activation and inflammatory factors increased significantly. Intrathecal injection (IT) of A-317491 significantly prolonged the bladder voiding intervals in CYP-4h, CYP-48h, CYP-10d, CYP-30d, and CYP-45d rats (P<0.01), and the maximal voiding pressure of the CYP-4h, CYP-48h, CYP-10d, CYP-30d, and CYP-45d groups was significantly decreased (P<0.05), while the maximal voiding pressure of the CYP-10d group was not significantly affected.
P2X3 receptors in dorsal root ganglion (DRG) play an important role in bladder function induced by intraperitoneal injection of CYP in rats. IT of P2X3 inhibitors can significantly improve the grade of bladder voiding dysfunction and chronic pelvic pain.
嘌呤能受体P2X3在病理性膀胱功能障碍和慢性盆腔疼痛中的作用尚不清楚。我们旨在通过环磷酰胺（CYP）诱导的间质性膀胱炎（IC）大鼠模型研究P2X3对膀胱功能的影响。
将120只雌性Sprague-Dawley（SD）大鼠随机分为6组：对照组、CYP-4h组、CYP-48h组、CYP-10d组、CYP-30d组和CYP-45d组。对照组注射生理盐水。CYP-4h组和CYP-48h组大鼠给予单次高剂量。CYP-10d组、CYP-30d组和CYP-45d组大鼠每三天重复给予低剂量CYP。采用尿动力学技术测量膀胱排尿功能，以观察P2X3受体对CYP诱导的IC大鼠膀胱功能的影响。
与对照组相比，CYP-4h组大鼠膀胱活动明显亢进，膀胱排尿间隔缩短（P<0.01），最大排尿压力升高（P<0.01）。同时，CYP-48h组、CYP-10d组、CYP-30d组和CYP-45d组膀胱过度活动程度逐渐加重，膀胱排尿间隔逐步缩短（P<0.01），最大排尿压力逐步升高（P<0.01）。与对照组相比，CYP-48h组主要表现为膀胱排尿间隔缩短（P<0.01）、排尿量降低以及膀胱内肥大细胞和炎症因子激活增加。在CYP-10d组，膀胱肥大细胞激活和炎症因子显著增加。鞘内注射（IT）A-317491可显著延长CYP-4h组、CYP-48h组、CYP-10d组、CYP-30d组和CYP-45d组大鼠的膀胱排尿间隔（P<0.01），CYP-4h组、CYP-48h组、CYP-10d组、CYP-30d组和CYP-45d组的最大排尿压力显著降低（P<0.05），而CYP-10d组的最大排尿压力未受到显著影响。
背根神经节（DRG）中的P2X3受体在大鼠腹腔注射CYP诱导的膀胱功能中起重要作用。鞘内注射P2X3抑制剂可显著改善膀胱排尿功能障碍和慢性盆腔疼痛的程度。
