脊髓细胞外信号蛋白调节激酶5在吗啡依赖大鼠戒断反应中的作用  

Role of extracellular signal-regulated protein kinase 5 in spinal cord in withdrawal responses in morphine-dependent rats

作　　者：王春光[1] 丁彦玲[1] 郭淑琴[1] 田祥[1] 殷树欣 张励才[2] 

机构地区：[1]保定市第一中心医院麻醉科,071000 [2]江苏省麻醉学重点实验室

出　　处：《中华麻醉学杂志》2013年第10期1212-1214,共3页Chinese Journal of Anesthesiology

基　　金：国家自然科学基金（30871307）;江苏省自然科学基金（BK2012580）

摘　　要：目的 探讨脊髓细胞外信号调节蛋白激酶5（ERK5）在吗啡依赖大鼠戒断反应中的作用.方法 取鞘内置管成功的成年雄性SD大鼠96只,体重200 ～ 250 g,采用随机数字表法,将其分为4组（n=24）：对照组（A组）、戒断组（B组）、二甲基亚砜组（C组）、ERK5抑制剂BIX02188组（D组）.B组、C组和D组皮下注射吗啡,首日10 mg/kg,第2～5天每日增加10 mg/kg,第6天注射50 mg/kg,建立大鼠吗啡依赖模型,A组给予等容量生理盐水,不制备吗啡依赖模型.B组末次注射吗啡后4h腹腔注射纳洛酮4 mg/kg,建立吗啡戒断模型.D组腹腔注射纳洛酮前1h鞘内注射ERK5抑制剂BIX0218810出,C组鞘内注射等容量溶媒1％二甲基亚砜.腹腔注射纳洛酮后1h内进行戒断反应评分和戒断所致的痛觉过敏评分.痛觉过敏评分测定完毕后,处死大鼠,取脊髓组织,测定ERK5和磷酸化ERK5（p-ERK5）的表达水平.结果 与A组比较,B组、C组和D组戒断反应评分和痛觉过敏评分升高,脊髓p-ERK5表达上调（P＜0.05）;与B组比较,D组戒断反应评分和痛觉过敏评分降低,脊髓p-ERK5表达下调（P＜0.05）,C组上述指标差异无统计学意义（P＞0.05）.结论 脊髓ERK5参与了吗啡依赖大鼠的戒断反应.Objective To evaluate the role of extracellular signal-regulated protein kinase 5 （ERK5） in the spinal cord in withdrawal responses in morphine-dependent rats.Methods Ninety-six adult male SpragueDawley rats in which intrathecal catheters were successfully placed,weighing 200-250 g,were randomly divided into 4 groups （n =24 each） using a random number table：normal saline group （group A）,withdrawal group （group B）,dimethyl sulfoxide （DMSO） group （group C） and ERK5 inhibitor BIX02188 group （group D）.Morphine dependence （MD） was induced by increasing doses of subcutaneous morphine for 6 days.The initial dose of morphine was 10 mg/kg once a day and was increased by 10 mg/kg once a day from the 2nd to 5th days until 50 mg/kg on the 6th day in B,C and D groups.Morphine withdrawal response （MW） was induced by intraperitoneal naloxone 4 mg/kg at 4 h after last morphine administration in B,C and D groups.In addition,BIX02188 and 1％ DMSO 10 μl were injected intrathecally at 1 h before naloxone injection in D and C groups,respectively.MW and morphine withdrawal-induced hypemlgesia were scored.The rats were then sacrificed after hyperalgesia was scored and the spinal cord was removed for determination of ERK5 and phosphorylated ERK5 （p-ERK5） expression.Results Compared with group A,MW and hyperalgesia scores were significantly increased and the expression of pERK5 was up-regulated in B,C and D groups （P ＜ 0.05）.Compared with group B,MW and hyperalgesia scores were significantly decreased and the expression of p-ERK5 was down-regulated in D group （P ＜ 0.05）,and no significant change was found in group C （P ＞ 0.05）.Conclusion ERK5 in the spinal cord is involved in withdrawal responses in morphine-dependent rats.

关 键 词：细胞外信号调节MAP激酶类 吗啡依赖 物质戒断综合征 脊髓 

分 类 号：R363[医药卫生—病理学]