不同剂量右美托咪定预注对利多卡因神经毒性的影响

Effects and possible mechanism of different doses dexmedetomidine pretreatment on lidocaine toxicity to nervus centralis of albino rabbit

目的比较不同剂量右美托咪定（dexmedetomidine，Dex）预注对利多卡因致白兔中枢神经毒性的影响及可能机制。方法将40只新西兰白兔按随机数字表法分为4组（A、B、C、D组），每组10只：A组通过颈内静脉泵人含Dex10μg／kg的生理盐水8ml，10min后以4mg·kg^-1·min^-1泵入利多卡因直到出现惊厥；B组泵人含Dex5μg／kg的生理盐水8ml，同法泵入利多卡因；c组泵入等量生理盐水，同法泵入利多卡因；D组只泵人生理盐水8ml。于白兔晾厥时抽血测利多卡因浓度，记录利多卡因剂量及发生惊厥时间，测脑组织天冬氨酸（aspartate，Asp）、谷氨酸（glutamicacid，Glu）、甘氨酸（glycine，Gly）、1-氨基丁酸（γ-aminobutyric acid，GABA）的含量。结果产生中枢神经毒性所需利多卡因剂量、利多卡因血药浓度及发生惊厥时间，A组[分别为：（240±48）mg，（6．4±0．8）μg／kg，（822±122）s]、B组[分别为：（230_＋51）mg，（6．3±0．5）μg／kg，（802±114）s]较C组[分别为：（137±37）mg，（5．4±0．6）μg／kg，（510±76）S]明显增加，差异有统计学意义（尸〈0．05）；Asp、Glu、Gly、GABA的含量，A组[分别为：（3．5±1．0）、（4．0±1．9）、（10．1±1．9）、（16．5±2．2）μmol／g]、B组[分别为：（3．7±0．8）、（4．2±1．9）、（11．4±2．2）、（17．4±2．4）μmol／g]、C组[分别为：（4．7±1．0）、（6．8±1．9）、（13．7±1.9）、（20．9±3，4）μmol／g]明显高于D组[分别为：（1．5±0．8）、（2．4±1．2）、（4．7±1．6）、（5．7±2．8）μmol／g]，差异有统计学意义（P〈0．05），而C组又明显高于A、B组（P〈0．05o结论预注Dex可以延缓利多卡因致惊厥反应的发生，增加利多卡因神经毒性的阈值，对中枢神经有一定的保护作用。

Objective To investigate the effects and possible mechanism of different doses dexmedetomidine （Dex） pretreatment on lidocaine toxicity to nervus centralis of albino rabbit. Methods Forty New-Zealand albino rabbit were randomly divided into 4 groups （n=10）. Group A and B were received infusion of 8 ml mixture Dex （respectively, 5μg/kg and 10μg/kg） and saline, 10 rain later lidocaine was pumped at the rate of 4 mg,kg^-1·min^-1 until occurrence of hyperspasmia. The equal dosis of saline and lidocaine were given in group C, but group D were only received saline. The hematoptasma density of lidocaine was measure when hyperspasmia occurred, the doses of lidocaine, the appearing times of lidocaine-induced hyperspasmia were observed, the concentration of aspar tate, glutamic acid, glycine and γ-aminobutyric acid in brain architecture were recorded. Results Compared with group C [（137±37） rag, （5.4±0.6）μg/kg, （510±76） s, respectively], the doses of lidocaine when neurotoxicity occur, the plasmic density of lidocaine and the appearing times of lidocaine-induced hyperspasmia were all increased obviously in group A [（240±48） rag, （6.4±0.8）μg/kg, （822±122） s, respectively] and B [（230±51） nag, （6.3±0.5） μg/kg, （802±114） s, respectively] （P〈0.05）. Compared with group D [（1.5±0.8）, （2.4±1.2）, （4.7±1.6）, （5.7±2.8）μmol/g, respectively], the concentration of aspartate, glutamic acid, glycine and gamma-aminobutyric acid in brain architecture were all increased in group A [（3.5±1.0）, （4.0±1.9）, （10.1±1.9）, （16.5±2.2）μmol/g, respectively], B[（3.7±0.8）, （4.2±1,9）, （11.4±2.2）, （17.4±2.4）μmol/g, respectively] and C[（4.7±1.0）, （6.8±1.9）, （13.7±1.9）, （20.9±3.4）μmol/g, respectively]（P〈0.05）, then in group C obviously higher than in group A and B （P〈0.05）.