Department of Urology, Graduate School of Medicine, Jeju National University, Jeju, South Korea.
Department of Urology, Bucheon St. Mary's hospital, College of Medicine, The Catholic University of Korea, Sosa-Ro 327, Wonmi-gu, Bucheon-si, Gyeonggi-do, Seoul, 14647, South Korea.
BMC Urol. 2017 Dec 29;17(1):121. doi: 10.1186/s12894-017-0313-4.
This study investigated changes in the expression of cannabinoid (CB) receptors and the effects of CB1 and CB2 agonists on detrusor overactivity (DO) associated with bladder outlet obstruction (BOO) in rats.
Male Sprague Dawley rats were randomly assigned to four groups (n = 10) in each group. The control group comprised sham-operated rats. A animals in the BOO, CB1 agonist and CB2 agonist groups all underwent BOO surgery. Three weeks postoperatively, cystometrography (CMG) was performed on all rats. After confirming the presence of DO in the CB1 and CB2 agonist groups, a CB1 agonist (WIN 55,212-2) and a CB2 agonist (CB65) were instilled intravesically, and CMG was repeated. CMG parameters, including the contraction interval (CI) and contraction pressure (CP) were then analyzed. The bladders of rats in all four groups were excised following CMG. Immunofluorescence staining and Western blotting were performed to localize CB1 and CB2 and measure their expression levels in the urothelium and detrusor muscle.
The CI was significantly longer and the CP was significantly lower in the CB1 agonist group than in the BOO group. CI and CP in the CB2 agonist group showed the same results. CB1 receptor immunofluorescence staining signals and immunoreactive bands in Western blotting were increased in the BOO group compared with results in the control group. Similarly, results for the CB2 receptor were also increased in the BOO group, although this difference was not significant. The CMG parameters in the BOO group were significantly improved by the inhibitory effects of CB1 and CB2 agonists on BOO-associated DO. The expression of CB1 was significantly increased in the urothelium and detrusor muscle in BOO-associated DO, but no significant change in CB2 expression was observed.
CB1 and CB2 receptors, especially CB1, play a role in the pathophysiology of BOO-associated DO, and could serve as therapeutic targets.
本研究旨在探讨大麻素（CB）受体表达的变化，以及 CB1 和 CB2 激动剂对膀胱出口梗阻（BOO）相关逼尿肌过度活动（DO）的影响。
雄性 Sprague Dawley 大鼠随机分为 4 组（每组 10 只）。对照组为假手术组。A 组动物均行 BOO 手术。3 周后，对所有大鼠进行膀胱测压。在确认 CB1 和 CB2 激动剂组存在 DO 后，向膀胱内注入 CB1 激动剂（WIN 55,212-2）和 CB2 激动剂（CB65），并重复进行膀胱测压。分析收缩间隔（CI）和收缩压（CP）等膀胱测压参数。所有 4 组大鼠均在进行膀胱测压后切除膀胱。进行免疫荧光染色和 Western blot 分析以定位 CB1 和 CB2，并测量其在上皮和逼尿肌中的表达水平。
与 BOO 组相比，CB1 激动剂组的 CI 明显延长，CP 明显降低。CB2 激动剂组的 CI 和 CP 也出现了相同的结果。与对照组相比，BOO 组的 CB1 受体免疫荧光染色信号和 Western blot 免疫反应性条带增加。同样，BOO 组的 CB2 受体也增加，但差异无统计学意义。CB1 和 CB2 激动剂对 BOO 相关 DO 的抑制作用使 BOO 组的 CMG 参数得到显著改善。在 BOO 相关 DO 中，CB1 的表达在上皮和逼尿肌中显著增加，但 CB2 的表达没有明显变化。
CB1 和 CB2 受体，特别是 CB1，在 BOO 相关 DO 的病理生理学中发挥作用，可作为治疗靶点。
