氯胺酮对喹啉酸诱导的大鼠纹状体毁损的保护作用

Protective effect of Ketamine on the quinolinic acid-induced lesion in a rat model of Huntington＇ s disease

目的观察不同剂量氯胺酮对喹呆酸（QA）诱导的亨廷顿病（HD）大鼠纹状体损伤的保护作用。方法将30只雌性SD大鼠随机分为3组，均予注射QA毁损单侧纹状体，其中两组采用不同剂量氯胺酮麻醉，另一组采用异氟烷吸入麻醉作为对照，3组大鼠注射QA的时间和剂量均相同，两周后，对大鼠进行步移实验和楼梯实验，随后行灌注和免疫组织化学分析。结果与氯胺酮比较，异氟烷麻醉组大鼠在行为学实验中表现出的功能缺陷更为明显，纹状体损害体积更大。此外，不同剂量氯胺酮麻醉组之间差异有统计学意义（P〈0．05），大剂量氯胺酮组大鼠纹状体毁损体积较小剂量氯胺酮组为小，行为学上表现出的功能缺失也相对较轻。结论氯胺酮能减轻兴奋毒性所致大鼠纹状体损害，可被视作一种潜在的QA兴奋毒性保护剂，其保护作用与应用剂量明显相关。

Objective As a non-competitive NMDA receptor antagonist, Ketamine is a commonly used anaesthetic agent. Quinolinic acid （QA） is a glutamate analogue that exerts its excitotoxic effect also via the NMDAR. We tested the QA lesion effect under the conditions of various dosage of Ketamine, to explore the protective effect of Ketamine on the QA-induced striatal lesion. Methods Thirty SD females were unilaterally lesioned using QA： two group were anaesthetised with different dose of ketamine and the other with isoflurane. The surgical coordinates and the dosage of QA were identical. Two weeks post-lesion, the animals were tested on stepping test, and staircase test, followed by perfusion, imnmnohistochemical and volumetric analysis. Results The isoflurane group, compared with the ketamine groups, showed larger striatal lesions and significant differences in other behavioral measurements reflecting the extent of the lesion （ P 〈 0. 05 ）. Beside, there were statistically differences between these two ketamine groups in aspect of lesion volume and behavioral performances. Conclusion The use of ketamine anaesthesia in the excitotoxic model can effectively alleviate the development of the lesion and it works in a dosedependent way.