中文摘要：

目的研究Anandamide（ANA）-大麻受体Ⅰ（CB1）在内脏高敏感形成中的作用及其机制。方法采用鸡卵清蛋白（OVA）腹腔注射基础致敏,联合非伤害性/伤害性结直肠扩张刺激（NNCRD/NCRD）,建立内脏高敏感性-NNCRD/NCRD大鼠模型。54只SD大鼠随机分为正常对照组（n=7）,生理盐水＋结直肠扩张（CRD）组（n=7）,OVA＋CRD＋二甲亚枫（DMSO）组（n=8）,OVA＋CRD＋不同剂量（0.5、5.0、10.0mg/kg）N-花生四烯酸氨基乙醇（ANA）组（n=8）,OVA＋CRD＋ANA＋AM251（选择性CB1受体拮抗剂）组（n=8）。采用免疫荧光组化及激光扫描共聚焦技术研究各组大鼠脊髓CB1阳性产物的分布特征及受体表达情况。根据腹壁肌电活动曲线下面积（AUC）评估内脏敏感性的变化。结果在80mmHg下行NCRD后,在L4-L6脊髓背角组织中,生理盐水＋CRD组、OVA＋CRD＋DMSO组CB1受体表达明显增加（P〈0.05）;与生理盐水＋CRD组比较,OVA＋CRD＋DMSO组CB1表达量明显增加（P〈0.05）。在20mmHg压力下行NNCRD时,各组大鼠内脏运动反射（VMR）AUC比较差异无统计学意义（P〉0.05）。在80mmHg压力下行NCRD时,生理盐水＋CRD组VMR-AUC较OVA＋CRD＋DMSO组明显降低（P〈0.05）,OVA＋CRD＋ANA（高剂量）组VMR-AUC较OVA＋CRD＋DMSO组明显降低（P〈0.05）,而OVA＋CRD＋ANA＋AM251组较OVA＋CRD＋ANA（高剂量）组VMR-AUC明显增加（P〈0.05）。结论 ANA可缓解OVA基础致敏联合NCRD诱导的伤害性刺激作用,该作用是通过CB1受体介导的,提示ANA-CB1系统参与了内脏高敏感的调控过程。

英文摘要：

Objective To investigate the role of anandamide（ANA）-mediated cannabinoid receptor I（CB1） on the acquisition of visceral hypersensitivity in rats, and explore its underlying mechanism. Methods The visceral hypersensitivity non-noxious/noxious colorectal distension （NNCRD/NCRD） model of rat was reproduced by ovalbumin （OVA） sensitization combined with NNCRD/NCRD. Fifty-four rats were randomly divided into control group （n=7）, saline＋CRD group （n=7）, OVA＋CRD＋dimethyl sulfoxide （DMSO） group （n=8）, OVA＋CRD＋different concentrations of ANA （0.5, 5.0, 10.0mg/kg） groups （8 each）, and OVA＋CRD＋ANA＋AM251 group （n=8）. The expression and quantitative assessment of CB1 were monitored by immunoflurorescence and laser scanning confocal analysis. The visceral sensitivity was evaluated by the area under curve （AUC） of myoelectrical activity of abdominal wall muscle. Results By NCRD at 80mmHg, the density of CB1 immunofluorescence intensity was significantly higher in L4-L6 of the spinal cord of the rats in saline＋CRD group compared with that in control group （P〈0.05）. The expression of CB1 was higher in OVA＋CRD＋DMSO group than in saline＋CRD group （P〈0.05）. By NNCRD at 20 mmHg, no statistical difference was found in the AUC ofvisceromotor reflex （VMR） among various groups （P〉0.05）. By NCRD at 80mmHg, the VMR-AUC increased obviously in OVA＋CILD＋DMSO group as compared with that of saline＋CRD group, but it decreased significantly in OVA＋CRD＋high concentration ANA group （P〈0.05）. When AM251 was intravenously given, VMR-AUC increased significantly in OVA＋CRD＋ANA＋AM251 group compared with that in OVA＋CRD＋different concentrations of ANA groups （P〈0.05）. Conclusions Intravenous administration of ANA may mitigate the visceral nociception induced by basic OVA- sensitization combined with NCRD stimulation in CB 1-mediated manner. It indicated that anandamide-mediated CB 1 cannabinoid receptor may regulate the developme