八肽胆囊收缩素及其受体拮抗剂对吗啡戒断大鼠脑内CaMK Ⅱ蛋白表达的影响  

Effects of CCK-8 and its receptor antagonists on CaMK Ⅱ expression of morphine withdrawal rats

作　　者：张雅静[1,2] 文迪[1] 杨胜昌[1] 于峰[1] 马春玲[1] 丛斌[1] 

机构地区：[1]河北医科大学法医系河北省法医学重点实验室,河北石家庄050017 [2]石家庄市第一医院肿瘤内科,河北石家庄050011

出　　处：《中国药理学通报》2016年第3期327-331,共5页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81273337;30672355);河北省应用基础研究重点研究项目(No 10966911D)

摘　　要：目的观察八肽胆囊收缩素(CCK-8)、CCK-1受体拮抗剂L-364,718及CCK-2受体拮抗剂LY-288,513对吗啡戒断大鼠额叶皮质、海马、纹状体细胞内钙/钙调蛋白依赖性的蛋白激酶Ⅱ(CaMKⅡ)表达的影响。方法建立吗啡依赖及纳洛酮催促戒断大鼠模型,观察CCK-8、L-364,718及LY-288,513对吗啡依赖大鼠戒断症状的影响;采用Western blot方法检测上述脑区CaMKⅡ蛋白表达的变化。结果①CCK-8、L-364,718及LY-288,513能明显改善吗啡依赖大鼠戒断症状的发生;②与盐水对照组相比,吗啡依赖组大鼠额叶皮质、海马、纹状体细胞内CaM KⅡ蛋白表达明显升高;纳洛酮催促戒断后上述脑区CaM KⅡ蛋白表达较吗啡依赖组均明显降低;③CCK-8、L-364,718及LY-288,513均使吗啡戒断大鼠额叶皮质、海马及纹状体内CaMKⅡ蛋白表达升高。结论 CaMKⅡ参与了吗啡依赖及戒断的形成,CCK-8及其受体拮抗剂抑制吗啡依赖大鼠戒断反应的机制可能与其对相关脑区CaMKⅡ蛋白表达的调节有关。Aim To observe the effects of CCK-8 and its receptor antagonists(L-364,718; LY288,513) on CaMK Ⅱ expression in prefrontal cortex(PFC),hippocampus(Hip) and cauduate putamen(CPu) of morphine withdrawal rats.Methods A physical morphinedependent model in rats was established by subcutaneous injection of morphine in gradually increasing doses for 5 consecutive days.The expression of CaMK Ⅱ in prefrontal cortex,hippocampus and striatum of rats was assayed by Western blot.Results ①CCK-8 and its receptor antagonists could relieve the morphine withdrawal symptoms of the rats.② Compared with control group morphine dependence increased CaMK Ⅱexpression in prefrontal cortex,hippocampus and striatum.Following naloxone precipitation,CaMK Ⅱ expression significantly decreased.③CCK-8 and its receptor antagonists pre-treatment significantly increased CaMK Ⅱexpression in prefrontal cortex(PFC),hippocampus and striatum of morphine withdrawal rats.Conclusion The inhibitory effect of CCK-8 and its receptor antagonists on withdrawal syndrome of morphine-dependent rats may be related to the increase of CaMK Ⅱ expression in specific brain regions.

关 键 词：八肽胆囊收缩素 L-364 718 LY288 513 吗啡依赖 吗啡戒断 钙/钙调蛋白依赖性的蛋白激酶Ⅱ 

分 类 号：R-332[医药卫生] R322.81