大鼠脊髓内大麻素CB2受体在芍药苷拮抗吗啡镇痛耐受中的作用  

Involvement of the rat spinal cannabinoid receptor 2 in inhibition of morphine antinociceptive tolerance by paeoniflorin

作　　者：宋扬[1] 赵昱[2] 曾凡荣[3] 李轶聪[2] 

机构地区：[1]佳木斯大学临床医学院,佳木斯154000 [2]解放军第211医院麻醉科,哈尔滨150080 [3]佳木斯大学附属第一医院麻醉科,佳木斯154000

出　　处：《神经解剖学杂志》2016年第5期635-640,共6页Chinese Journal of Neuroanatomy

基　　金：全军医学科技"十二五"科研课题(CWS11J006)

摘　　要：目的:探讨脊髓内大麻素CB2受体在芍药苷拮抗大鼠慢性吗啡镇痛耐受中的作用。方法:成功鞘内置管清洁级Sprague-Dawley(SD)大鼠60只,随机分为4组(n=15):生理盐水组(NS组),吗啡组(MOR组),芍药苷组(PF组)和吗啡+芍药苷组(MOR+PF组)。连续7 d鞘内注射吗啡(15μg)建立慢性吗啡耐受的动物模型。采用50℃热水甩尾潜伏期法(tail flick latency,TFL)和机械反射阈值法(mechanical withdrawal threshold,MWT)观察鞘内注射芍药苷对吗啡镇痛耐受的影响;应用免疫组织荧光染色法检测芍药苷对腰段脊髓小胶质细胞活化的影响;应用免疫印迹法检测芍药苷对腰段脊髓CB2表达的影响。结果:连续7 d鞘内注射吗啡后,与NS组比较,MOR组大鼠腰段脊髓背角小胶质细胞显著增多,腰段脊髓CB2表达显著增加(P<0.05);而与MOR组比较,MOR+PF组大鼠腰段脊髓背角小胶质细胞显著减少,腰段脊髓CB2表达显著减少(P<0.05)。与MOR组7 d大鼠最大镇痛效应百分率(percent of maximal possible potential effect,MPE)比较,MOR+PF组大鼠MPE显著增加(TFL:19%±4%vs 41%±3%;MWT:18%±6%vs 42%±4%,P<0.05)。结论:芍药苷能显著拮抗大鼠慢性吗啡镇痛耐受,其作用机制可能与抑制脊髓内CB2受体表达增加有关。Objective： To investigate the role of spinal CB2 in attenuation of chronic morphine antinociceptive tolerance by Paeoniflorin（ PF）. Methods： Sixty male Sprague-Dawley rats with successful intrathecal catheter were randomly divided into four groups（ n = 15） ： Saline group（ NS）; Morphine group（ MOR）; Paeoniflorin group（ PF）; Morphine plus Paeoniflorin group（ MOR ＋ PF）. A morphine tolerance model was induced by intrathecal injection of morphine 15 μg once daily for 7 consecutive days. The effect of Paeoniflorin on morphine antinociceptive tolerance was explored by MPE TFL and MPE MWT. Immunohistochemistry assay was applied to detect the expression of IBA-1. Western Blot was used to evaluate the change of spinal CB2 expression. Results： After 7 d of repeated intrathecal injection of morphine,the expressions of IBA-1 and CB2 in MOR group were significantly up-regulated as compared with NS group（ P〈0. 05）,While the expressions of IBA-1 and CB2 in MOR ＋ PF group were significantly down-regulated as compared with MOR group（ P〈0. 05）. On day 7 after intrathecal injection of morphine,MPE were significantly increased in MOR ＋ PF group than in MOR group（ TFL： 19% ± 4% vs 41% ± 3%; MWT： 18% ± 6% vs 42% ± 4%,P〈0. 05）. Conclusion： Paeoniflorin significantly attenuated chronic morphine antinociceptive tolerance in rats. Inhibition of spinal CB2 may be one of the mechanisms underlying the blocking of morphine tolerance by Paeoniflorin.

关 键 词：吗啡镇痛耐受 芍药苷 CB2 脊髓 大鼠 

分 类 号：R614[医药卫生—麻醉学]