胆碱和对乙酰氨基酚的协同镇痛作用及其机制  

Mechanism of the synergistic analgesic effect between choline and acetaminophen

作　　者：张卫东[1] 郭梦倬 张娜[1] 王汝欢[3] 汪海[3] 冯泽国[1] 

机构地区：[1]解放军总医院麻醉手术中心,北京100853 [2]北京清华长庚医院麻醉科,北京102218 [3]军事医学科学院卫生学环境医学研究所,北京100850

出　　处：《药学学报》2017年第8期1262-1267,共6页Acta Pharmaceutica Sinica

基　　金：国家重点基础研究发展计划(973计划)资助项目(2012CB518200);军队“十二五”重大专项资助项目(AWS11J003)

摘　　要：探讨胆碱(Cho)与对乙酰氨基酚(Ace)的协同镇痛作用及其机制。本研究采用腹腔注射0.6%醋酸溶液建立小鼠醋酸扭体疼痛模型。将KM小鼠随机分为对照组(n=10)、单用Cho组(n=50)、单用Ace组(n=50)和合用组(n=40),造模后计数20 min内扭体次数。采用Origin Pro8.5软件分析求得各药物的ED50。采用等辐射分析法分析Cho和Ace的相互作用。为进一步研究Cho和Ace协同作用的机制,将40只KM小鼠随机分为生理盐水对照组(control组)、Cho组、Ace组和Cho+Ace组,每组10只。造模后,小鼠眼球取血,使用ELISA试剂盒分别测定小鼠血清中TNF-α、IL-6、PGE2、NF-κB的含量。经计算可得,单用Cho组和单用Ace组的ED50分别为19.47和20.56 mg·kg^(-1),合用组ED50为Cho 2.94 mg·kg^(-1)+Ace 3.15 mg·kg^(-1)。等辐射分析法证实Cho与Ace合用时具有协同镇痛作用。ELISA结果发现Cho组和Ace组血清中TNF-α、IL-6、PGE2和NF-κB含量较control组降低(P<0.05),而与Cho组和Ace组相比,Cho+Ace组TNF-α、IL-6、PGE2和NF-κB含量进一步降低,且差异具有统计学意义(P<0.05)。本研究证实Cho与Ace具有协同镇痛作用,其机制可能与抑制NF-κB信号通路的激活有关。This study was designed to investigate the synergistic analgesic effect between choline（Cho） and acetaminophen（Ace）. Mice were treated with 0.6% acetic acid solution by intraperitoneal injection to build acetate writhing model. The KM mice were randomly divided into four groups： control group（n = 10）, Cho group（n = 50）, Ace group（n = 50）, combination group（Cho＋Ace group, n = 40）, then the writhing times were counted respectively. Origin Pro8.5 was used to calculate ED50. The isobolographic analysis was used to test the interaction of Cho and Ace. To explore the mechanism, forty KM mice were randomly divided into control group, Cho group, Ace group and Cho ＋ Ace group. Blood was collected for detection of TNF-α, IL-6, PGE2 and NF-κB content using ELISA kits. The result ED50 was calculated as followings. ED50 of Cho and Ace was 19.47 mg·kg^-1 and 20.56 mg·kg^-1. The concentrations were 2.94 mg·kg^-1 for Cho and 3.15 mg·kg^-1 for Ace in the combination test. The levels of TNF-α, IL-6, PGE2 and NF-κB in Cho group and Ace group were lower than those in the control group（P〈0.05）. Compared to the Cho group and Ace group, the levels of TNF-α, IL-6, PGE_2, NF-κB in Cho ＋ Ace group were reduced further（P〈0.05）. The results revealed that Cho and Ace have synergistic analgesic effects, which may associate with inhibition of the NF-κB signaling pathway.

关 键 词：胆碱 对乙酰氨基酚 镇痛 核因子ΚB 

分 类 号：R963[医药卫生—微生物与生化药学]