山西医科大学学报Issue(3)：211-215,216,6.DOI:10.13753/j.issn.1007-6611.2015.03.005
黑皮质素受体拮抗剂对大鼠吗啡耐受及脊髓小胶质细胞激活的影响
Effect of melanocortin receptor antagonist on morphine tolerance and microglial activation in spinal cord of rats
马加贵 1安建雄 1褚海辰 2李喜元 1董河 2李灯凯 1张春芳1
作者信息
- 1. 航空总医院麻醉与重症医学科，北京100012
- 2. 青岛大学附属医院麻醉科
- 折叠
摘要
Abstract
Objective To investigate the effect of melanocortin receptor antagonist HS014 on morphine tolerance and microglial activa-tion in the spinal cord of rats. Methods Thirty adult male SD rats were randomly divided into 5 groups( n=6 in each group) . The rats were injected with morphine(10 mg/kg,intraperitoneal administration)twice daily for 5 consecutive days in morphine group(M), and normal saline in N group. In HS014+morphine( HM) group and saline+morphine( NM) group,the rats were respectively injected in-trathecally with 5 μg of HS014 and 5 μl of saline 15 min before the second administration of morphine at each testing day. In HS014+saline( HN) group,the rats were injected intrathecally 5 μg of HS014 15 min prior to the second saline injection for 5 consecutive days. The withdrawal latency was measured by the hot-plate test 30 min after the second administration at each testing day. At day 5, the immu-nohistochemical technique was used to evaluate the microglial activation by examining positive cells of ox-42. Results At day 1 and 2, the paw withdrawal latency was higher in M group than in N group(P<0. 001). At day 3,the paw withdrawal latency began to decrease in M group, and there was no significant difference between M group and N group at day 5(P>0. 05). At day 3-5, the paw withdrawal la-tency was increased in HM group compared with M group(P<0. 05). Compared with N group, the OX-42 positive cells increased in the spinal cord in M group(P<0. 001). Compared with M group, the microglia activation was suppressed, and the OX-42 positive cells de-creased in the spinal cord in HM group(P<0. 001). Conclusion Chronic administration of morphine(10 mg/kg, twice daily for 5 d) could induce morphine tolerance and microglial activation in the spinal cord of rats. Combined administration of HS014 and mor-phine could inhibit the development of morphine tolerance and microglial activation,but HS014 alone could not show analgesic effect.关键词
黑皮质素受体/HS014/吗啡耐受/OX-42Key words
melanocortin receptor/HS014/morphine tolerance/OX-42分类
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马加贵,安建雄,褚海辰,李喜元,董河,李灯凯,张春芳..黑皮质素受体拮抗剂对大鼠吗啡耐受及脊髓小胶质细胞激活的影响[J].山西医科大学学报,2015,(3):211-215,216,6.
