【摘要】 背景:胞外信号调节激酶(extracellularsignal-regulatedkinases,ERK)由其特异的上游激酶丝裂原活化蛋白激酶和胞外信号调节激酶激酶(MAPK/ERKkinases,MEK)激活,是细胞生长、记忆和长时程神经元可塑性中的一个重要因素。目的:研究ERK在慢性压迫性损伤引起的神经痛形成和维持中的作用。设计:以实验动物为研究对象,随机对照的验证性研究。单位:一所大学医院的麻醉科。材料:实验于2003-09/2004-06在江苏省麻醉医学研究所完成,选择雄性清洁级SD大鼠115只,体质量220～300g,由徐州医学院实验动物中心提供,分笼饲养,室温维持20～25℃,自然照明,自由饮水和摄食。干预:慢性压迫性损伤(chronicconstrictioninjury,CCI)模型建立后第5天,采用Mestre直接鞘内注射方法行不同浓度的U0126注射,同时在对照组给予鞘内注射无菌的50g/L二甲基亚砜。主要观察指标:采用vonFrey纤维丝和热痛刺激仪观察CCI大鼠鞘内应用U0126后机械性痛敏和热痛敏阈值的变化,同时应用免疫组织化学和免疫印记方法观察对大鼠脊髓背角内ERK活性的影响。结果:CCI引起大鼠脊髓背角内ERK活性的增强,鞘内注射U0126抑制ERK活性的同时能明显减轻由CCI导致的大鼠机械性痛敏和热痛敏。结论:脊髓背角内细胞外信号调节激酶的激活和转位与CCI引起的神经痛的形成和更多还原

【Abstract】 BACKGROUND:The extracellular signal related kinase(ERK) cascade is activated by its specific upstream kinase MAPK/ERK kinase(MEK) and identified as a critica l regulator of cell growth,memory formation and long term neuronal plasticity. OBJECTIVE:To investigate the role of ERK activation in establishment and maint enance of chronic neuropathic pain. DESIGN:A randomized controlled experiment based on the animals. SETTING:Department of Anesthesiology of a university affiliated hospital. MATERIALS:The experiment was performed in the Medical Institute of Anesthesiol ogy of Jiangsu Province from September 2003 to June 2004.Totally 115 male clean SD rats weighting 220 to 300 g were provided by the Experimental Animal Center o f Xuzhou Medical College.The rats were raised in separate cages with natural lig hting at 20 to 25 ℃,having free access to food and water. INTERVENTIONS:Five days after chronic constrictive injury(CCI) model was estab lished,different doses of U0126 were intrathecally injected according to Mestre’ s method.The control group received sterile intrathecal injection of 50 g/L dime thylsulfoxide. MAIN OUTCOME MEASURES:①Changes in mechanical and thermal hyperalgesia by usin g von Frey filaments and thermal hyperalgesia stimulator at different time point s after intrathecal injection of U0126;②Effect on activation and translocation of ERK in spinal cord dorsal horn by immunohistochemistry and Western blot analy sis. RESULTS:CCI could increase the activity of EPK in spinal cord dorsal horn.Intr athecal injection of U0126 significantly attenuated CCI induced mechanical and thermal hyperalgesia. CONCLUSION:Activation and translocation of ERK contribute to formation and mai ntenance of CCI induced neuropathic pain.更多还原