罗哌卡因、布比卡因和利多卡因对小鼠中枢神经系统毒性作用的比较(英文)  

Effect of neurotoxicity of ropivacaine,bupivacaine and lidocaine on central nervous system of mice

作　　者：金小高[1] 罗爱林[1] 王金韬[1] 

机构地区：[1]华中科技大学同济医学院附属同济医院麻醉科,湖北省武汉市430030

出　　处：《中国临床康复》2005年第45期145-147,共3页Chinese Journal of Clinical Rehabilitation

摘　　要：背景:有证据表明罗哌卡因导致的心脏毒性比相同剂量的布比卡因低,但布比卡因脂溶性高,且作用强度大,临床上只需较小的剂量即可。中枢神经系统明显的神经毒性作用(如惊厥)往往是心脏毒性产生的先兆,半数致死剂量和半数致惊厥剂量的比值能够反应局麻药的安全性。目的:确定罗哌卡因、布比卡因、利多卡因的半数致惊厥剂量和半数致死量,比较在引起50%致惊厥反应率时3种酰胺类局部麻醉药对中枢神经系统的毒性作用。设计:随机对照,3个实验各自独立。单位:华中科技大学同济医学院附属同济医院麻醉科。材料:实验于2002-07/12在武汉华中科技大学同济医学院附属同济医院麻醉科实验室完成。选取1月龄雄性昆明小白鼠310只,清洁级。方法:①局麻药剂量与致惊厥率及致死率关系的确定:选择240只小鼠,确定罗哌卡因的量效关系时采取的小鼠数量为50只,分为76.80,68.69,61.44,49.15,31.46mg/kg5种剂量,10只/剂量组;确定布比卡因的量效关系时采取的小鼠数量为90只,分为50.00,47.29,44.72,42.29,40.00,35.78,32.00,28.62,25.60mg/kg9种剂量,10只/剂量组;确定利多卡因的量效关系时采取的小鼠数量为100只,分为183.11,163.77,146.48,131.02,117.19,93.75,75.00,60.00,48.00,38.40mg/kg10种剂量,10只/剂量组。不同剂量的局麻药腹腔注射时,尽量使每种麻醉药致各组小鼠的惊厥率和致死率对称分布在50%左右,给药5min后记录各组的致惊厥率和死亡率。使用Probit法将量效曲线直线化,建立3种局麻药的对数剂量一概率单位的回归直线方程,确定各自的量效关系。②不同剂量利多卡因对小鼠惊厥时间和大脑c-Fos表达的影响:选择40只小鼠,随机分成4组:空白对照组、30%致惊厥剂量组、60%致惊厥剂量组、90%致惊厥剂量组,10只/组。空白对照组腹腹腔注射生理盐水,利多卡因各剂量组依次腹腔注射47,57,73mg/kg的利多卡因,观察�BACKGROUND： It is demonstrated that ropivacaine has less toxicity than bupivacaine, but bupivacaine has higher liposolubility and efficacy, so a less dose of bupivacaine is needed in clinical comparing with ropivacaine. Serious convulsion is usually followed by cardiotoxicity induced by local anesthetics. The ratio of medial lethal dose （CD50） and median convulsant doses （LD50） is usually used to assess the comparative safety of local anesthetics. OBJECTIVE： To establish CD50 and LD50 of 2% lidocaine, 0.75% bupivacaine and 0.75% mpivacaine for Kunming mice and select proper indicator for neurotoxicity, then to compare neurotoxicity of the three local anesthetics on central nervous system. DESIGN： Randomized and controlled study. SETTING： Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology. MATERIALS： This study was carried out from July to December in 2002 in the Laboratory of Anesthesiology, Tongji Hospital, Tonji Medical College, Huazhong University of Science and Technology. Totally 310 Kunming mice aged of 1-month with clean grade were enrolled in this study. METHODS： （1） To determine the relation of dose of local anesthetics with conclusion rate and death rate in mice. To determine the dose-effect relationship for ropivacaine, 50 mice were selected and divided into 5 groups with 10rates in each group who received dose of 76.80, 68.69, 61.44, 49.15, 31.46 mg/kg respectively. For bupivacainc, 90 mice were divided into 9 groups, with 10 rates in each group who received intraperitoneal dose of 50.00, 47.29, 44.72, 42.29, 40.00, 35.78, 32.00, 28.62, 25.60 mg/kg respectively. For lidocairie, 100 mice were divided into 10 groups, with10rates in each group who received dose of 183.11, 163.77, 146.48, 131.02, 117.19, 93.75, 75.00, 60.00, 48.00, 38.40 mg/kg respectively. For each local anesthetic, the rates of convulsion or death were tried to distribute on both sides of 50% symmetrically. On the dose-response curve, 4 o

关 键 词：惊厥 酰胺类/投药和剂量 利多卡因 布比卡因 原癌基因蛋白质C-FOS类 

分 类 号：R338.2[医药卫生—人体生理学]