拮抗触液核细胞外信号调节蛋白激酶5对吗啡依赖大鼠戒断行为的影响  

Effect of inhibition of extracellular signal-regulated kinase 5 in cerebrospinal fluid-contacting nucleus on morphine withdrawal behavior in morphine-dependent rats

作　　者：王春光[1] 郭淑琴[1] 张志强[1] 丁彦玲[1] 殷树欣 陈宏伟[1] 张励才[2] 

机构地区：[1]保定市第一中心医院麻醉科,河北保定071000 [2]徐州医学院江苏省麻醉学重点实验室,江苏徐州221002

出　　处：《中国药理学通报》2014年第2期225-229,共5页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 30871307);江苏省自然科学基金资助项目(No BK2012580)

摘　　要：目的探讨触液核磷酸化细胞外信号调节蛋白激酶5（ERK5）在吗啡依赖大鼠戒断行为中的作用。方法成年♂sD大鼠48只，体质量230-270g，采用随机数字法，将大鼠随机分为两组（n=24）：吗啡-纳洛酮-DMSO组（A组）和吗啡-纳洛酮-BIX02188组（B组）。采用剂量递增法皮下注射吗啡以建立大鼠吗啡依赖模型，d 6上午经腹腔注射纳洛酮，催促戒断症状出现，即建立吗啡戒断模型。采用行为药理学方法结合免疫荧光技术，侧脑室内注射ERK5特异性抑制剂BIX02188，观察其对吗啡依赖大鼠戒断行为、戒断所致痛觉过敏及触液核p-ERK5表达的影响。结果与吗啡-纳洛酮-DMSO组相比，吗啡一纳洛酮．BIX02188组大鼠跳跃、咬牙、湿狗样抖动、腹泻及体重减轻等戒断症状明显缓解（P〈0．05），而扭体、流涎无改善（P〉0．05）；戒断所致痛觉过敏明显减轻（P〈0．05）。与吗啡一纳洛酮-DMSO组相比，吗啡一纳洛酮-BIX02188组大鼠触液核p-ERK5阳性神经元数量明显减少（P〈0．05）。结论拮抗触液核ERK5可减轻吗啡依赖大鼠戒断症状，提示触液核ERK5参与吗啡依赖大鼠戒断症状的表达。Aim To investigate the effect of phosphor-extraeellular signal-regulated kinase 5 （ERK5） in ce-rebrospinal fluid-contacting nucleus on morphine with- drawal behavior in morphine-dependent rats. Methods Forty-eight male adult SD rats weighing 230 - 270 g were randomly divided into 2 groups （ n = 24 ） ： mor- phine-naloxone-DMSO group （Group A ） and mor- phine-naloxone-BIX02188 group （ Group B ）. Rats were subcutaneously injected with morphine. On day 6, rats were injected with naloxone （intraperitoneal） to precipitate morphine withdrawal syndrome. To identify the function of ERK5 in morphine withdrawal, mor-phine withdrawal-like behaviorM test and immunofluo- rescence technique were used in this research. Thescores of morphine withdrawal symptom, morphine withdrawal-induced allodynia and the activation of ERK5 in cerebrospinal fluid-contacting nucleus were observed after lateral ventricle injection of BIX02188. Result Compared with morphine-naloxone-DMSO group, the withdrawal symptoms such as jumping, teeth chatting, wet dog shakes, diarrhea and weight loss were attenuated in morphine-naloxone-BIX02188 group （ P 〈 0. 05 ）, while, writhing and salivation were not improved （ P 〉 0. 05 ） ; the morphine withdrawal-induced allodynia was significantly decreased in mor-phine-naloxone-BIX02188 group （ P 〈 0. 05 ）. The number of p-ERK5 in cerebrospinal fluid-contacting nucleus was significantly decreased in morphine-halo-xone-BIX02188 group compared with morphine-nalox- one-DMSO group （P 〈 0.05）. Conclusion Inhibition of ERK5 in cerebrospinal fluid-contacting nucleus can relieve the withdrawal symptoms, which indicates the activation of ERK5 in cerebrospinal fluid-contacting nucleus contributs to the expression of withdrawalsymptoms in morphine-dependent rtas.

关 键 词：吗啡依赖 戒断症状 触液核 远位触液神经元 细胞外信号调节蛋白激酶5 BIX02188 

分 类 号：R-332[医药卫生] R322.81