不同剂量氯胺酮对大鼠急性脊髓损伤的影响

Effects of different doses of ketamine on acute spinal cord injury in rats

目的研究不同剂量氯胺酮对大鼠急性脊髓损伤(SCI)的影响及其可能机制。方法 SpragueDawley大鼠60只,将其随机分入假手术组、损伤组、5mg/kg氯胺酮组、10mg/kg氯胺酮组和20mg/kg氯胺酮组,每组12只。除假手术组仅做椎板切除外,其余各组均制作SCI模型。氯胺酮各组于SCI后4h给予相应剂量的氯胺酮,假手术组和损伤组以相同的方法给予等量的0.9%氯化钠溶液。观察各组大鼠脊髓组织形态学变化,并进行组织形态学分级。分别采用黄嘌呤氧化酶法和硫代巴比妥酸法测定血浆超氧化物歧化酶(SOD)和丙二醛(MDA)水平,采用BBB(Basso,Beattie and Bresnahan)评分评价大鼠的后肢功能。结果损伤组中形态学分级为3级的大鼠比例显著高于假手术组、10mg/kg氯胺酮组和20mg/kg氯胺酮组(P值分别<0.01、0.05),SCI后72h时的平均血浆MDA水平显著高于假手术组、10mg/kg氯胺酮组和20mg/kg氯胺酮组同时间点(P值分别<0.01、0.05),SCI后72h时的平均血浆SOD水平和SCI后7、14、21和28d的BBB评分均显著低于假手术组、10mg/kg氯胺酮组和20mg/kg氯胺酮组同时间(P值分别<0.01、0.05)。结论 SCI后4h给予10或20mg/kg氯胺酮可以减轻SCI,其机制可能与氯胺酮的抗氧化作用有关。

Objective To explore the effects of different doses of ketamine on acute spinel cord injury （SCI） in rats and possible mechanism. Methods Sixty Sprague-Dawley rats were randomly divided into sham operation group, injury group, 5 mg/kg ketamine group, 10 rng/kg ketamine group and 20 mg/kg ketarnine group （ n = 12 each）. The rats in the sham operation group underwent laminectomy, and the rats in the other groups were made SCI models. Four hours later, the rats in ketamine groups were treated with corresporcling doses of drug, while sham group and injury group received the same amount of normal saline in the same way. Tissue morphology and histological grade of spinel cord were observed. Plasma superoxide disrnutase （SOD） and malonaldehyde （MDA） were detected by xanthine oxidase method and thioberbituric acid method, respectively. The neurological function of hind limb was evaluated by BBB （Basso, Beattie and Bresnahan） scales. Results Compared with those in sham operation group, 10 mg/kg ketamine group and 20 mg/kg ketamine group, the proportion of rats with histological grade three and MDA level were significantly increased in injury group 72 hours after SCI （P〈0.01, 0.05）, while SOD activity at 72 hours after SCI and BBB scores on days 7, 14, 21 and 28 after SCI were significantly deceased in injury group （P 〈 0.01, 0.05）. Conclusion SCI can be ameliorated when ketamine （10 mg/kg and 20 mg/kg） is given 4 hours after SCI, which is possibly related to its antioxidation effect.