MK-801对利多卡因致大鼠惊厥效应的影响  

Effect of MK-801 on seizure induced by lidocaine in Rats

作　　者：陈丽丽[1] 张山[1] 乔玉敏[1] 赵三军[1] 

机构地区：[1]河北医科大学第二医院麻醉科,石家庄市050000

出　　处：《临床麻醉学杂志》2011年第8期812-814,共3页Journal of Clinical Anesthesiology

基　　金：教育部"留学归国人员科研启动基金"项目(教外司留[2005]383号);河北省科技攻关项目(编号052761254)

摘　　要：目的研究MK-801对利多卡因致大鼠中毒惊厥作用及其机制。方法 Wistar雄性大鼠22只,随机分为对照组(C组,n=6)、利多卡因组(L组,n=8)和MK-801组(M组,n=8)。C组腹腔注射生理盐水0.5 ml/kg,30 min后泵入复方乳酸钠。L组和M组腹腔分别注射生理盐水0.5ml/kg和MK-801 0.5 mg/kg,30 min后静注2%利多卡因2 mg,继以4 mg.kg-1.min-1持续泵入,惊厥波出现后停止泵入利多卡因,记录惊厥波发生及持续时间,呼吸抑制及持续时间。观察N-甲基-D-天门冬氨酸受体1(NMDAR1)免疫阳性细胞活性变化,测定泵注后20、30、40、50、60 min海马CA1区细胞外液谷氨酸(Glu)和γ-氨基丁酸(GABA)浓度。结果 C组未出现惊厥波,L组均出现惊厥波,M组2只大鼠出现惊厥波。与L组比较,M组呼吸抑制出现较晚(P<0.05),呼吸抑制持续时间较短(P<0.05)。与C组比较,L组和M组NMDAR1免疫阳性细胞数均显著增多(P<0.05),L组显著多于M组(P<0.05)。泵注后30、40、50、60 min L组Glu浓度显著高于C组和M组(P<0.05)。L组GABA浓度仅在泵注后40 min时较C组和M组明显升高(P<0.05),其它时点差异无统计学意义。结论 MK-801可抑制利多卡因中毒惊厥效应,其抑制作用可能与NMDAR1活性降低有关。Objective To investigate the effect of MK-801 on the convulsion induced by lidocaine and the underlying mechanisms in rats. Methods Twenty-two male Wistar rats weighing 250 ±20 g were randomly divided into 3 groups： control group（group C, n= 6）; lidocaine group（group L,n=8） ; MK-801 group（group M,n=8）. Group C. normal saline was injected intraperitoneally at a dose of 0. 5 ml/kg for 30 min followed by sodium lactate infusion. In group L and M, 0. 5 ml/kg normal saline and 0. 5 mg/kg MK-801 was intraperitoneally injected respectively for 30 min, then 2% lidocaine hydrochloride 2 mg was administered intravenously and was maintained with a rate of 4 mg·kg^-1 ·min^-1 until the multiple sharp waves were seen on EEG. The time when convulsion waves or respiratory depression appeared and disappeared was recorded. The expression of N-methy-Daspartate receptor 1 （NMDAR1） in rats＇ brain was observed using immunohistochemical staining. The dialysate of hippocampal CA1 field was stored for determining the concentration of Glu and GABA 20, 30, 40, 50 and 60 min after perfusion. Results No high spike waves appeared on EEG in group C. Each rat in group L, but only two rats in group M were found of high spike waves. Compared with group L, respiratory depression occurred later and lasted shorter in group M （P〈 0. 05）. Compared with group C, the expression of NMDAR1 in hippocampal CA1 field was significantly higher in both group L and group M （P〈0. 05）, while the expression of NMDAR1 in group M was significantly lower than that in group L （P〈0. 05）. Compared with group C and group M, the Glu concentration at the time of 30, 40, 50 and 60 min after infusion and the GABA Concentration only at 40 min after infusion was higher in group L （P〈0.05） Conclusion MK-801 plays a positive role in the convulsion induced by lidocaine, and the decrease in the activity of NMDAR may be involved in the mechanism.

关 键 词：利多卡因 惊厥MK-801 NMDA受体 

分 类 号：R965[医药卫生—药理学]