氯胺酮麻醉对大鼠局灶性脑缺血模型病理结局的影响

背景:大鼠局灶性脑缺血模型的制作需要在麻醉状态下通过外科手术完成,但麻醉药物可能影响局灶性脑缺血的结局。目的:观察氯胺酮麻醉对大鼠局灶性脑缺血模型病理结果的影响,并与戊巴比妥进行对照。设计:随机对照动物实验。单位:西安交通大学医学院实验动物中心和西安交通大学医学院第二附属医院病理科。材料:实验于2004-05/2005-03在西安交通大学医学院实验动物中心和第二附属医院病理科进行。取30只雄性SD大鼠,单纯随机分为戊巴比妥组和氯胺酮组,每组15只。方法:戊巴比妥组和氯胺酮组大鼠分别以戊巴比妥40mg/kg,氯胺酮60mg/kg腹腔麻醉。待翻正反射消失后,通过腔内线栓永久性阻塞大鼠大脑中动脉引发脑缺血。主要观察指标:①大脑中动脉阻塞4h时,参照改良的Bederson’s评分方法进行神经功能缺陷评分。②大脑中动脉阻塞24h时,每组选取5只大鼠,处死后取脑,以20g/L的TTC进行染色,计算梗死体积。③大脑中动脉阻塞72h,记录2组死亡率。然后每组取4只大鼠,采用相应的麻醉剂进行麻醉后处死取脑,甲苯胺蓝染色检测半暗带内的存活神经元。结果:30只大鼠全部进入结果分析。①大脑中动脉阻塞4h时,戊巴比妥组和氯胺酮组神经病学评分差异不显著(1.46±0.98,1.38±0.68,P>0.05)。②大脑中动脉阻塞24h时氯胺酮组的脑梗死体积小于戊巴比妥组犤(28.1±4.11)%,(37.8±4.95)%,P<0.05犦。③大脑中动脉阻塞72h,戊巴比妥组和氯胺酮组死亡率差异不显著(42%比33%,P>0.05),但半暗带内的神经元密度氯胺酮组高于戊巴比妥组犤(836±15),(740±24)个/mm2,P<0.05犦。结论:①在制作大鼠局灶性脑缺血模型时,氯胺酮麻醉下产生较轻的脑损伤。②在氯胺酮麻醉下制作的大鼠局灶性脑缺血模型中评价一些药物或方法的神经保护作用时,所研究的药物或方法的神经保护作用可能难以体现。

Influence of ketamine anesthesia on the pathological outcome of focal cerebral ischemia model in rats

BACKGROUND: Focal cerebral ischemia model in rats should be established under drugged state by surgery operation, but anaesthetic drug may influence the outcome of focal cerebral ischemia.OBJECTIVE: To observe the effects of ketamine anesthesia on the pathological outcome of focal cerebral ischemia model in rats, and perform control with pentobarbital.DESIGN: Randomized controlled animal experiment.SETTING: Center of Experimental Animal and Department of Pathology of Second Affiliated Hospital, School of Medicine, Xi'an Jiaotong University.MATERIALS: The experiment was performed in the Center of Experimental Animal and Department of Pathology of Second Affiliated Hospital,School of Medicine, Xi'an Jiaotong University from May 2004 to March 2005. Thirty male SD rats were randomly assigned into pentobarbital group and ketamine group with 15 rats in each group.METHODS: The rats in the pentobarbital group and ketamine group were subjected to 40 mg/kg pentobarbital and 60 mg/kg ketamine by abdominal anaesthesia, respectively. The permanent middle cerebral artery occlusion (MCAO) was performed in rats by thread embolism in cavity in order to induce cerebral ischemia after abolition of righting reflex.MAIN OUTCOME MEASURES: ①A modified Bederson's scoring system was adopted to determine the neurological functional deficit at hour 4 after the MCAO. ②Five rats from each group were selected at hour 24 after MCAO. They were killed and their brain was stained with 20 g/L 2,-3,-5-triphenyltetrazolium hydrochloride (TTC). The infarct volume was determined. ③ MCAO was performed for 72 hours and mortality rate of two groups were recorded. Four rats in each group were re-anesthetized. They were killed and their brain was gained. Survival neurons were detected with toluidine blue staining.RESULTS: Totally 30 rats were involved in the result analysis. ①There was no significant difference in neurological score 4 hours after MCAO between pentobarbital group and ketamine group (1.46±0.98,1.38±0.68 ,P＞0.05). ②The infarct volume in the ketamine group was less than that in the pentobarbital group at hour 24 after MCAO [(28.1±4.11)%,37.8±4.95]%, P＜0.05]. ③The mortality rate 72 hours after ischemia was not significantly different between pentobarbital group and ketamine group (42% vs 33%,P＞0.05). But neuron density in penumbra in the ketamine group was higher than that in the pentobarbital group [(836±15),(740±24) numbers/mm2, P＜0.05].CONCLUSION: ①The ketamine anesthesia induces minor brain injury in setting of the focal cerebral ischemia model in rats. ②When neuroprotective effects of procedures or drugs being studied are evaluated in this focal cerebral ischemia model, they might provide no additional advantage to cerebral ischemia.