Zhang Hui-ping, Li Cui-ling, Lu Peng, Zheng Jia-cui, Yu Li-li, Yang Wei-min, Xiong Fei, Zeng Xiao-yong
Family Planning Research Institute, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China.
World J Urol. 2014 Feb;32(1):91-7. doi: 10.1007/s00345-013-1098-z. Epub 2013 May 12.
The purpose of the study is to explore the function of P2X3 and NK1 receptors antagonists on cyclophosphamide (CYP)-induced cystitis in rats.
Sixty female Sprague-Dawley (SD) rats were randomly divided into three groups. The rats in the control group were intraperitoneally (i.p.) injected with 0.9% saline (4 ml/kg); the rats in the model group were i.p. injected with CYP (150 mg/kg); and the rats in the intervention group were i.p. injected with CYP with subsequently perfusion of bladder with P2X3 and NK1 receptors' antagonists, Suramin and GR 82334. Spontaneous pain behaviors following the administration of CYP were observed. Urodynamic parameters, bladder pressure-volume curve, maximum voiding pressure (MVP), and maximum cystometric capacity (MCC), were recorded. Pathological changes in bladder tissue were observed. Immunofluorescence was used to detect the expression of P2X3 and NK1 receptors in bladder.
Cyclophosphamide treatment increased the spontaneous pain behaviors scores. The incidence of bladder instability during urine storage period of model group was significantly higher than intervention group (χ(2) = 7.619, P = 0.007) and control group (χ(2) = 13.755, P = 0.000). MCC in the model group was lower than the control and intervention groups (P < 0.01). Histological changes evident in model and intervention groups rats' bladder included edema, vasodilation, and infiltration of inflammatory cells. In model group, the expression of P2X3 receptor increased in urothelium and suburothelium, and NK1 receptor increased in suburothelium, while the expression of them in intervention group was lower.
In CYP-induced cystitis, the expression of P2X3 and NK1 receptors increased in urothelium and/or suburothelium. Perfusion of bladder with P2X3 and NK1 receptors antagonists ameliorated the bladder function.
本研究旨在探讨P2X3和NK1受体拮抗剂对环磷酰胺（CYP）诱导的大鼠膀胱炎的作用。
将60只雌性Sprague-Dawley（SD）大鼠随机分为三组。对照组大鼠腹腔注射0.9%生理盐水（4 ml/kg）；模型组大鼠腹腔注射CYP（150 mg/kg）；干预组大鼠腹腔注射CYP，随后用P2X3和NK1受体拮抗剂苏拉明和GR 82334灌注膀胱。观察注射CYP后的自发疼痛行为。记录尿动力学参数、膀胱压力-容积曲线、最大排尿压力（MVP）和最大膀胱容量（MCC）。观察膀胱组织的病理变化。采用免疫荧光法检测膀胱中P2X3和NK1受体的表达。
环磷酰胺处理增加了自发疼痛行为评分。模型组储尿期膀胱不稳定的发生率显著高于干预组（χ(2)=7.619，P=0.007）和对照组（χ(2)=13.755，P=0.000）。模型组的MCC低于对照组和干预组（P<0.01）。模型组和干预组大鼠膀胱的组织学变化包括水肿、血管扩张和炎性细胞浸润。模型组中，P2X3受体在上皮和上皮下表达增加，NK1受体在上皮下表达增加，而干预组中它们的表达较低。
在CYP诱导的膀胱炎中，P2X3和NK1受体在上皮和/或上皮下的表达增加。用P2X3和NK1受体拮抗剂灌注膀胱可改善膀胱功能。
