Honda Masashi, Yoshimura Naoki, Kawamoto Bunya, Kobayashi Naoto, Hikita Katsuya, Muraoka Kuniyasu, Saito Motoaki, Sejima Takehiro, Chancellor Michael B, Takenaka Atsushi
Department of Urology, Tottori University Faculty of Medicine, 36-1 Nishi, Yonago, 683-8504, Japan.
Int Urol Nephrol. 2014 Oct;46(10):1953-9. doi: 10.1007/s11255-014-0734-x. Epub 2014 May 14.
To investigate the effects of activation of sensory neuron-specific receptors (SNSRs) on cyclophosphamide (CYP) bladder overactivity in rats.
Female Sprague-Dawley rats (235-258 g) were used. Rats were injected with either CYP (200 mg/kg, intraperitoneally) or saline (control). Continuous cystometrograms (0.04 ml/min) were recorded 48 h after CYP or saline injection under urethane anesthesia. After stable micturition cycles were established, a selective rat SNSR1 agonist, bovine adrenal medulla 8-22 (BAM8-22), was administered intravenously or intrathecally.
Cyclophosphamide treatment-induced higher baseline pressure and shorter intercontraction intervals compared with the control group. Intravenous administration of BAM8-22 at 10, 30 and 100 μg/kg significantly increased intercontraction intervals in the CYP-treated group. Intrathecal administration of BAM8-22 at 0.03, 0.1 and 0.3 μg also significantly increased intercontraction intervals in the CYP-treated group. Intravenous or intrathecal administration of BAM8-22 did not change baseline pressure or maximum voiding pressure in the CYP-treated group.
These findings indicate that activation of SNSRs can suppress CYP-induced bladder overactivity, probably due to suppression of bladder afferent activity.
研究激活感觉神经元特异性受体(SNSRs)对环磷酰胺(CYP)诱导的大鼠膀胱过度活动的影响。
使用雌性Sprague-Dawley大鼠(235 - 258克)。大鼠腹腔注射CYP(200毫克/千克)或生理盐水(对照组)。在乌拉坦麻醉下,于注射CYP或生理盐水48小时后记录连续膀胱内压图(0.04毫升/分钟)。在建立稳定的排尿周期后,静脉内或鞘内给予选择性大鼠SNSR1激动剂牛肾上腺髓质8 - 22(BAM8 - 22)。
与对照组相比,环磷酰胺治疗导致更高的基线压力和更短的收缩间期。在CYP治疗组中,静脉注射10、30和100微克/千克的BAM8 - 22显著增加了收缩间期。鞘内注射0.03、0.1和0.3微克的BAM8 - 22也显著增加了CYP治疗组的收缩间期。静脉或鞘内注射BAM8 - 22并未改变CYP治疗组的基线压力或最大排尿压力。
这些发现表明,激活SNSRs可抑制CYP诱导的膀胱过度活动,可能是由于抑制了膀胱传入活动。