不同剂量右美托咪定对兔脊髓的神经毒性

Experimental study of dexmedetomidine toxicities on rabbit spinal neurons

目的观察不同剂量右美托咪定复合0.75%布比卡因硬膜外镇痛的神经毒性作用。方法选择硬膜外置管成功后的健康家兔25只,雌雄不拘,重2.0-3.0kg,随机均分为五组。对照组（C组）：生理盐水1.5ml;B组：0.75%布比卡因1 ml＋生理盐水0.5 ml;D1、D2、D3组0.75%布比卡因1ml＋右美托咪定0.1、0.2、0.4μg/kg。硬膜外连续给药3d,继续观察至第7天处死家兔,作光镜和电镜检查。结果电镜下各组兔脊髓均未见破坏性病变。光镜下D2组有1只,D3组有2只兔的脊髓病变较严重,灰质和白质分界不清,脊髓灰质坏死,神经细胞减少。结论硬膜外给予右美托咪定对兔脊髓和脊神经存在剂量相关性损伤,但本研究剂量硬膜外注药后兔下肢运动功能可完全恢复。

Objective To observe the neurotoxicity of epidural different dose of dexmedetomidine in combination with 0.75% bupivacaine.Methods Twenty-five rabbits weight 2-3kg without gender tendency and equipped with an epidural lumbar catheter were allocated randomly to five groups with 5cases each.The control group（group C）received injections of 1.5 ml normal saline,0.75%bupivacaine 1.5ml plus normal saline 0.5ml in group B,and the other treatment groups received injections of 0.75% bupivacaine 1 ml plus dexmedetomidine 0.1 μg/kg（group D1）,0.75%bupivacaine 1 ml plus dexmedetomidine 0.2μg/kg（group D2）or 0.75% bupivacaine 1 ml plus dexmedetomidine 0.4μg/kg（group D3）,in the same volume of 1.5ml.After successive 3-day epidural administration of the drugs and a 3-day observation,the rabbits were killed and the spinal cord was examined under optical and electron microscope.Results Serious damages of neuron were found in 1animal from group D2 and 2from group D3 under optical microscope.There was unclear boundaries between gray and white matter.Some nerve cells appeared necrosis in the grey matter of spinal cord and the number of nerve cells was decreased.Some reversible changes were found in all groups under electron microscope.Conclusion Epidural administration of dexmedetomidine can induce spinal cord and spinal nerves injury dose-dependently,and the motor function can recuperated completely.