Treatment with a cannabinoid receptor 2 agonist decreases severity of established cystitis.
Treatment with a cannabinoid receptor 2 agonist decreases severity of established cystitis.
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DOI：
10.1016/j.juro.2013.10.102
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发表时间：
2014-04
影响因子：
6.6
通讯作者：
Bjorling, Dale E.
中科院分区：
文献类型：
--
作者：
Wang, Zun-Yi;Wang, Peiqing;Bjorling, Dale E.
关键词：
我们研究了选择性大麻素受体 2 激动剂 GP1a 治疗是否会改善实验性膀胱炎的严重程度。我们通过膀胱内滴注丙烯醛在小鼠中建立膀胱炎后确定了牵涉性痛觉过敏与尿频增加之间的关联。通过向雌性 C57BL/6NH 小鼠膀胱内滴注丙烯醛诱导膀胱炎。滴注丙烯醛后3.5、22和30小时，用GP1a（10 mg/kg腹腔注射）或载体治疗小鼠。测试小鼠后爪的机械敏感性。通过量化自由活动小鼠的尿斑来评估短期自愿排尿。收集膀胱、称重并进行处理以进行免疫组织化学、组织学和免疫印迹分析。丙烯醛滴注后48小时，所有小鼠的膀胱均显示出炎症的组织学证据。大麻素受体 2 激动剂治疗动物的水肿严重程度和膀胱重量增加受到抑制（p <0.05）。膀胱炎或 GP1a 或 AM630（选择性大麻素受体 2 拮抗剂）加 GP1a 治疗似乎都不会改变尿路上皮中大麻素受体 2 样免疫反应性的丰度。丙烯醛治疗后机械敏感性显着增加，而大麻素受体 2 激动剂治疗小鼠的机械敏感性增加减弱（p <0.05）。使用丙烯醛后，小直径尿斑的数量显着增加，并且用 GP1a 处理减弱了这种增加（p <0.05）。 AM630 可以防止 GP1a 效应。用选择性大麻素受体2激动剂治疗可降低已确定的丙烯醛诱导的膀胱炎的严重程度，并抑制与机械敏感性增加和膀胱尿频增加相关的膀胱炎症。我们的数据表明大麻素受体 2 是治疗疼痛性炎症性膀胱疾病的潜在治疗靶点。
We investigated whether treatment with the selective cannabinoid receptor 2 agonist GP1a would ameliorate the severity of experimental cystitis. We determined the association of referred hyperalgesia and increased urinary frequency after establishing cystitis in mice by intravesical instillation of acrolein. Cystitis was induced by intravesical instillation of acrolein in female C57BL/6NH mice. Mice were treated with GP1a (10 mg/kg intraperitoneally) or vehicle 3.5, 22 and 30 hours after instillation of acrolein. Mice were tested for mechanical sensitivity of hind paws. Short-term voluntary voiding was assessed by quantifying urine spots of freely moving mice. Bladders were collected, weighed and processed for immunohistochemical, histological and immunoblotting analysis. At 48 hours after acrolein instillation the bladder of all mice showed histological evidence of inflammation. The severity of edema and increase in bladder weight were inhibited in cannabinoid receptor 2 agonist treated animals (p <0.05). Neither cystitis nor treatment with GP1a or AM630 (selective cannabinoid receptor 2 antagonist) plus GP1a appeared to alter cannabinoid receptor 2-like immunoreactivity abundance in urothelium. Mechanical sensitivity was significantly increased after acrolein and the increase was attenuated in cannabinoid receptor 2 agonist treated mice (p <0.05). The number of small diameter urine spots was significantly increased after acrolein and treatment with GP1a attenuated this increase (p <0.05). GP1a effects were prevented by AM630. Treatment with a selective cannabinoid receptor 2 agonist decreased severity of established acrolein induced cystitis and inhibited bladder inflammation associated increased referred mechanical sensitivity and increased bladder urinary frequency. Our data indicate that cannabinoid receptor 2 is a potential therapeutic target for treatment of painful inflammatory bladder diseases.
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影响因子：
7.3
作者：
Horvath, Bela;Magid, Lital;Pacher, Pal
通讯作者：
Pacher, Pal
影响因子：
6.6
作者：
Tyagi, Vikas;Philips, Brian J.;Tyagi, Pradeep
通讯作者：
Tyagi, Pradeep
影响因子：
6.6
作者：
Gratzke, Christian;Streng, Tomi;Andersson, Karl-Erik
通讯作者：
Andersson, Karl-Erik
影响因子：
4.7
作者：
Kinsey, Steven G.;Mahadevan, Anu;Lichtman, Aron H.
通讯作者：
Lichtman, Aron H.
DOI：
10.1016/j.juro.2011.03.132
发表时间：
2011-08
期刊：
The Journal of urology
影响因子：
--
作者：
Berry SH;Elliott MN;Suttorp M;Bogart LM;Stoto MA;Eggers P;Nyberg L;Clemens JQ
通讯作者：
Clemens JQ