咪唑安定预先给药对罗哌卡因致大鼠中枢神经系统毒性反应的影响

Effect of midazolam pretreatanent on neurotoxicity of ropivacaine in rats

目的探讨咪唑安定预先给药对罗哌卡因致大鼠中枢神经系统毒性反应的影响及其机制。方法 SD大鼠30只,4-6月龄,体重250-300 g,随机分为3组(n=10):空白对照组(C组)、罗哌卡因组(R组)和咪唑安定+罗哌卡因组(MR组)。R组以0．5 ml/min速率静脉输注0．75％罗哌卡因,至大鼠出现惊厥时停药;MR组于输注罗哌卡因前5 min静脉注射咪唑安定0．8mg/kg;C组以0．5 ml/min速率输注生理盐水2ml。停止输注罗哌卡因后即刻处死大鼠,取静脉血1 ml,测定pH值,并用紫外比色法测定乳酸浓度;用高效液相色谱技术测定脑组织谷氨酸(Glu)、天冬氨酸(Asp)、甘氨酸 (Gly)和γ-氨基丁酸(GABA)的含量。结果与C组比较,R组静脉血乳酸浓度增加,pH值降低,MR、R 组大鼠惊厥时脑组织各种氨基酸含量均升高(P<0．05);与R组比较,MR组大鼠惊厥时罗哌卡因剂量增加,静脉血乳酸浓度降低,脑组织Asp、Gly和GABA含量降低(P<0．05)。结论咪唑安定预先给药可预防罗哌卡因对大鼠中枢神经系统的毒性,并通过降低脑组织兴奋性氨基酸的水平,降低罗哌卡因致中枢神经系统毒性反应的程度。

Objective To investigate the preventive effect of midazolam pretreatment against neurotoxicity of ropivacaine and the underlying mechanism. Methods Thirty male SD rats aged 4-6 months weighing 250-300 g were randomly divided into 3 groups with 10 animals in each group： group Ⅰ blank control; group Ⅱ ropivacaine （R） and group Ⅲ midazolam-ropivaeaine （M-R）. In group R and M-R 0.75% ropivaeaine was infused i.v. at a rate of 0.5 ml· min^-1 until the animal developed convulsion. The animals were killed and brains were immediately removed for determination of glutamate, aspartate, glycine and GABA content in the brain. Venous blood samples were taken for determination of pH and plasma concentration of lactate. The total amount of ropivacaine infused was calculated.Results The plasma lactate concentration was significantly higher and pH was significantly lower in group R than in blank control group. The concentrations of the 4 amino acids in the brain were significantly increased in group R and M-R as compared with the blank control group. The aspartate, glycine and GABA contents in the brain were significantly lower in M-R group than in R group. The total amount of ropivacaine infused i.v. was significant larger in group M-R than in group R. Conclusion Midazolam pretreatment can prevent the neurotoxicity of ropivacaine by modulating the balance between excitatory and inhibitory amino acids.