瑞替加滨对左旋布比卡因引起的中枢神经系统毒性的影响  

Effects of Retigabine on Central Nervous System Toxicity Induced by Levobupivacaine

作　　者：苑进革[1] 王志刚[1] 王新波[1] 程艳新 陈永学[1] YUAN Jin-ge;WANG Zhi-gang;WANG Xin-bo;CHENG Yan-xin;CHEN Yong-xue(Department of Anesthesiology,Handan Central Hospital,Handan 056008,China;Department of Pain,The Third Affiliated Hospital of Hebei Medical University,Shijiazhuang 050000,China)

机构地区：[1]邯郸市中心医院麻醉科,邯郸056008 [2]河北医科大学第三医院疼痛科,石家庄050000

出　　处：《科学技术与工程》2023年第20期8608-8613,共6页Science Technology and Engineering

基　　金：河北省医学科学研究课题计划(20130031)。

摘　　要：酰胺类局麻药布比卡因和罗哌卡因可以抑制KCNQ2/Q3通道,增加神经元的兴奋性。抗癫痫药瑞替加滨可以逆转布比卡因对KCNQ2/Q3通道的抑制作用。为观察KCNQ2/3钾离子通道激活剂瑞替加滨对局麻药左旋布比卡因诱发的兔中枢神经毒性的影响。通过将20只新西兰兔随机分为两组,瑞替加滨组(R组,样本数n=10)和对照组(C组,样本数n=10),每组10只。两组兔均并以8 mL/kg/h速度经耳缘静脉输注0.5%左旋布比卡因直至发生兔发生惊厥,惊厥后立即停止输注左旋布比卡因,R组静脉注射瑞替加滨5 mg/kg,C组静脉注射等体积的生理盐水作为对照。连续监测每只兔的行为特征和脑电波变,记录惊厥停止后30 min的兔脑电图和心电图,并进行定量脑电图分析。记录发生惊厥时输注左旋布比卡因所需时间,惊厥行为以及惊厥脑电波的持续时间,记录家兔基础心率、惊厥前以及给予瑞替加滨和生理盐水处理后30 min心率变化。实验结果表明:瑞替加滨能有效终止兔行为学和脑电波惊厥,减少行为学惊厥持续时间和脑电波(EEG)惊厥持续时间,并且降低惊厥后β和θ波功率。可见KCNQ2/3通道在左布比卡因诱导的中枢神经系统毒性中发挥重要作用,KCNQ2/3钾离子通道激活剂瑞替加滨可用于治疗左旋布比卡因诱导的惊厥。Amide local anesthetics bupivacaine and ropivacaine can inhibit KCNQ2/Q3 channels and increase neuronal excitability.Retigabine,an antiepileptic agent,reversed the inhibitory effect of bupivacaine on KCNQ2/Q3 channels.To observe the effect of retigabine,a KCNQ2/3 potassium channel activator,on central nervous system toxicity induced by levobupivacaine.Twenty New Zealand rabbits were randomly divided into two groups,rategabine group(R group,number of samples n=10)and control group(C group,number of samples n=10),with 10 rabbits in each group.Rabbits in both groups were also given 0.5%levobupivacaine via auricular vein at a rate of 8 mL/kg/h until the occurrence of convulsion.Levobupivacaine infusion was stopped immediately after convulsion.Group R was given 5 mg/kg retegabine intravenously,and group C was given equal volume of normal saline intravenously as control.The behavioral characteristics and EEG changes of each rabbit were continuously monitored,and the electroencephalogram and electrocardiogram of rabbits were recorded 30 min after convulsion stopped,and quantitative EEG analysis was performed.The time required for infusion of levobupivacaine during convulsion,the duration of convulsive behavior,and the duration of convulsive brainwaves were recorded.The basal heart rate,heart rate changes before convulsion and 30 min after treatment with rategabine and normal saline were recorded.The results show that rategabine can effectively stop behavioral and EEG convulsions,reduce the duration of behavioral convulsions and EEG convulsions,and reduce theβandθwave power after convulsion.The KCNQ2/3 channel plays an important role in levobupivacaine-induced central nervous system toxicity,and the KCNQ2/3 potassium channel activator rategabine can be used to treat levobupivacaine-induced convulsions.

关 键 词：KCNQ2/3通道 瑞替加滨 惊厥 局麻药中毒 

分 类 号：R614.3[医药卫生—麻醉学]