八肽胆囊收缩素对吗啡戒断大鼠蓝斑和中脑导水管周围灰质CREB及p-CREB的影响  

Effect of cholecystokinin octapeptide-8 on CREB and p-CREB in locus caeruleus and periaoueductal gray matter of morphine withdrawal rats

作　　者：杨胜昌[1] 文迪[1] 丛斌[1] 李英敏[1] 刘振江[1] 于海磊[1] 孟雁欣[1] 马春玲[1] 

机构地区：[1]河北医科大学基础医学院法医学系,河北省法医学重点实验室,石家庄050017

出　　处：《解剖学报》2012年第2期171-176,共6页Acta Anatomica Sinica

基　　金：国家自然科学基金资助项目(30672355);河北省自然科学基金资助项目(C2007000826);河北省应用基础研究重点基础研究资助项目(10966911D)

摘　　要：目的探讨八肽胆囊收缩素(CCK-8)及其受体拮抗剂对吗啡戒断症状的影响及其相应的信号转导机制。方法建立吗啡依赖及戒断动物模型,每组6只。应用改良柳田知司法对戒断症状评分,并采用免疫组织化学方法检测大鼠蓝斑和中脑导水管周围灰质内CREB及p-CREB的变化。结果腹腔及侧脑室注射CCK-8,CCK1及CCK2受体拮抗剂均可明显降低戒断症状评分;吗啡依赖后蓝斑和中脑导水管内p-CREB明显增高,戒断后蓝斑内p-CREB水平较依赖组进一步增高,而中脑导水管内p-CREB却较依赖组下降。腹腔及侧脑室注射CCK-8,CCK1及CCK2受体拮抗剂均可逆转戒断后中脑导水管内p-CREB的降低;腹腔及侧脑室注射CCK1及CCK2受体拮抗剂可逆转戒断后蓝斑内p-CREB的升高,而CCK-8却对蓝斑内p-CREB的表达无明显影响。结论CCK-8可通过对蓝斑和中脑导水管内p-CREB的调节减轻吗啡戒断症状,且表现出明显的脑区特异性。Objective To explore the effect of cholecystokinin octapeptide-8 （CCK-8） and its recepetor antagonists on morphine withdrawal and its signal transduction pathway. Methods Morphine dependent and withdrawal animal models were established, 6 rats for each group. Morphine withdrawal syndrome was observed and estimated by Gellert-Holtzman scale. The changes of CREB and p-CREB in the locus caeruleus （LC） and periaoueductal gray matter （PAG） were measured by immunohistochemical method. Results The withdrawal score was decreased by CCK-8 and its reeepetor antagonists through intraperitoneal （i. p） or intraeerebroventricular （i. v. c ） injection. Chronic morphine treatment increased p-CREB in LC and PAG. After withdrawal, p-CREB was further increased in LC but decreased in PAG. CCK-8 and its recepetor antagonists by i. p or i. v. e reversed changes of p-CREB in PAG after withdrawal, CCK-8 recepetor antagonists by i. p or i. v. c reversed changes of p-CREB in LC after withdrawal but had no effect by CCK- 8. Conclusion CCK-8 may inhibit the morphine withdrawal syndrome by modulating expression of p-CREB in LC and PAG, which is of obvious region-specificity.

关 键 词：八肽胆囊收缩素 CREB P-CREB 吗啡戒断 免疫组织化学 大鼠 

分 类 号：R971.1[医药卫生—药品]