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脊髓c-Jun在NMDA受体NR2B亚基介导的大鼠吗啡镇痛耐受中的作用
引用本文:傅璐,郭瑞鲜,莫利求,崔宇,赵春梅,胡芬,陈培熹,冯鉴强. 脊髓c-Jun在NMDA受体NR2B亚基介导的大鼠吗啡镇痛耐受中的作用[J]. 中国药理学通报, 2011, 27(2): 248-252
作者姓名:傅璐  郭瑞鲜  莫利求  崔宇  赵春梅  胡芬  陈培熹  冯鉴强
作者单位:1. 中山大学中山医学院生理学教研室,广东,广州,510080
2. 中山大学附属第一医院黄浦院区麻醉科,广东,广州,510080
3. 广东省东莞卫生学校,广东,东莞,523018
4. 中山大学中山医学院生理学教研室,广东,广州,510080;中山大学附属第一医院黄浦院区麻醉科,广东,广州,510080
基金项目:广东省科技计划资助项目
摘    要:目的探讨脊髓c-Jun在N-甲基-D-天冬氨酸(N-meth-yl-D-aspartate,NMDA)受体NR2B亚基介导的吗啡镇痛耐受中的作用。方法取Sprague-Dawley(SD)成年大鼠连续7 d鞘内注射吗啡10μl(1.5 g.L-1)建立慢性吗啡镇痛耐受模型。应用热水甩尾法测定甩尾潜伏期(疼痛指标)以观察痛反应变化。应用免疫组织化学染色法检测磷酸化c-Jun(p-c-Jun)和总c-Jun(t-c-Jun)的表达。结果鞘内注射吗啡7 d,可激活大鼠脊髓的c-Jun,表现为神经元内p-c-Jun表达升高;鞘内注射NR2B选择性拮抗剂10μl Ro256981(2 g.L-1)可以抑制慢性吗啡镇痛耐受时脊髓神经元c-Jun的激活,并明显拮抗吗啡镇痛耐受的形成。结论脊髓神经元c-Jun的磷酸化参与NMDA受体NR2B亚基介导的吗啡镇痛耐受。

关 键 词:吗啡镇痛耐受  神经元  N-甲基-D-天冬氨酸受体  NR2B亚基  c-Jun  JNK

Role of c-Jun of spinal cord in NMDA receptor subunit NR2B mediated morphine antinociceptive tolerance in rats
FU Lu,GUO Rui-xian,MO Li-qiu,CUI Yu,ZHAO Chun-mei,HU Fen,CHEN Pei-xi,FENG Jian-qiang. Role of c-Jun of spinal cord in NMDA receptor subunit NR2B mediated morphine antinociceptive tolerance in rats[J]. Chinese Pharmacological Bulletin, 2011, 27(2): 248-252
Authors:FU Lu  GUO Rui-xian  MO Li-qiu  CUI Yu  ZHAO Chun-mei  HU Fen  CHEN Pei-xi  FENG Jian-qiang
Affiliation:FU Lu1,GUO Rui-xian1,MO Li-qiu2,CUI Yu1,ZHAO Chun-mei3,HU Fen1,CHEN Pei-xi1,FENG Jian-qiang1,2(1.Dept of Physiology,Zhongshan Medical College,Sun Yat-sen University,Guangzhou 510080,China,2.Dept of Anesthesiology,Huangpu Division of the First Affiliated Hospital,3.Dept of Physiology,Dongguan Health School,Dongguan Guangdong 523018,China)
Abstract:Aim To investigate the role of spinal cord c-Jun in the development of N-methyl-D-aspartate(NMDA)receptor subunit NR2B mediated morphine antinociceptive tolerance.Methods Morphine 10 μl(1.5 g·L-1) was administered intrathecally for consecutive 7 days to achieve analgesic tolerance to morphine.Hot water tail flick test was used to assess the analgesic efficacy.Immunohistochemistry assay was applied to detect the expressions of phosphorylated c-Jun(p-c-Jun) and total c-Jun(t-c-Jun).Results At the 7th day of repeated intrathecal injection of morphine,c-Jun was activated remarkably in the lumbar spinal cord,which mainly existed in neurons.Repeated intrathecal injection of the NR2B competitive inhibitor Ro256981 10 μl(2 g·L-1)coadministrated with morphine not only partly inhibited the activation of c-Jun induced by chronic morphine treatment,but also markedly attenuated the development of morphine antinociceptive tolerance.Conclusion The spinal cord neuron p-c-Jun contributes to NMDA receptor subunit NR2B mediated morphine antinociceptive tolerance.
Keywords:c-Jun  JNK
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