慢性压迫损伤性神经病理性疼痛大鼠模型中脊髓背角ERK、CREB、BDNF表达的变化  

Expression of ERK, CREB and BDNF in spinal cord dorsal horn of rat model with chronic constriction injury-induced neuropathic pain

作　　者：徐良[1] 裘涛[2] 张丽娟[3] 张伟骏[2] 

机构地区：[1]浙江省人民医院重症医学科,杭州310014 [2]浙江中医药大学附属第一医院神经内科 [3]武警浙江总队杭州医院神经内科

出　　处：《浙江医学》2016年第16期1341-1344,共4页Zhejiang Medical Journal

基　　金：浙江省卫生厅项目(2013KYA139);浙江中医药管理局项目(2014ZB039);浙江中医药科技计划项目(2016ZB015)

摘　　要：目的通过建立慢性神经结扎性损伤(CCI)大鼠模型,揭示在神经病理性疼痛发生、发展过程中细胞外调节蛋白激酶(ERK)、环磷腺苷效应元件结合蛋白(CREB)、脑源性神经营养因子(BDNF)表达的变化。方法将21只大鼠随机双盲分为模型组、假手术组、U0126组,每组各7只,模型组及U0126组建立CCI模型,假手术组暴露坐骨神经不做结扎,3组均进行鞘内置管,U0126组鞘内注射阻断剂U0126 10μg/次,连续3d;模型组造模成功后、假手术组术后予0.9%氯化钠溶液0.12ml/kg灌胃至术后14d。对各组大鼠分别于术前、术后1、7、14d进行热痛觉过敏行为测试和机械刺激测试,采用Western blot法检测模型大鼠脊髓背角ERK、CREB、BDNF的表达水平。结果与假手术组相比,模型组大鼠术后热板及机械缩足反射阈值明显降低,差异均有统计学意义(均P<0.05)。CCI导致大鼠脊髓背角内胞浆与胞核内ERK、CREB、BDNF水平均增加,差异均有统计学意义(均P<0.01)。ERK阻滞剂U0126组能明显升高大鼠术后热板及机械痛敏阈值(P<0.05),U0126组导致大鼠脊髓背角内胞质与胞核内CREB、BDNF水平均明显降低,差异均有统计学意义(均P<0.05)。结论 CCI模型导致痛觉过敏,U0126可以减轻CCI大鼠的疼痛。ERK-CREB磷酸化的通路参与BDNF对于背根神经节的神经元的保护和修复过程。Objective To investigate the expression of extracellular signal- regulated kinase（ERK）, c AMP response element binding protein（CREB） and brain- derived neurotrophic factor（BDNF） in spinal cord dorsal horn of rat model with chronic constriction injury（CCI）- induced neuropathic pain. Methods CCI model was induced by chronic nerve ligation in rats.Twenty one rats were randomly divided into model group, sham operation group and U0126 group with 7 in each group. The thermal hyperalgesia and mechanical stimulation were tested; the expressions of ERK, CREB and BDNF protein in rat spinal cord dorsal horn were detected by Western blot. Results Compared with sham group, model group after the thresholds of thermal hyperalgesia and mechanical stimulation tests were significantly lower（P〈0.05）, and the expressions of ERK, CREB,and BDNF protein were significantly increased（P〈0.01）. ERK inhibitor U0126 significantly increased the thresholds of thermal hyperalgesia and mechanical stimulation tests（P〈0.05）, and also decreased the expressions of ERK, CREB and BDNF protein in spinal cord dorsal horn（P〈0.05）. Conclusion CCI leads to hyperalgesia in rats, U0126 can reduce the pain in CCI rats,which indicates that ERK- CREB phosphorylation pathway may be involved in the protection and repair of dorsal root ganglion neurons by BDNF.

关 键 词：脑源性神经营养因子 神经病理性疼痛 细胞外调节蛋白激酶 环磷腺苷效应元件结合蛋白 慢性神经结扎性损伤 

分 类 号：R741[医药卫生—神经病学与精神病学] R-332[医药卫生—临床医学]