异丙酚对氯胺酮所致大脑皮质神经元损害保护作用的机制  

Neuroprotective effects and mechanisms of propofol on neuronal damage induced by ketamine in rat posterior cingulate cortex

作　　者：郭建荣[1] 杜金满[1] 谢道奋[1] 任利远[1] 余雷霆[1] 李颂[1] 

机构地区：[1]宁波大学医学院附属李惠利医院麻醉科

出　　处：《中国临床药理学与治疗学》2005年第5期522-526,共5页Chinese Journal of Clinical Pharmacology and Therapeutics

摘　　要：目的:观察异丙酚对氯胺酮诱导的cfos基因在大鼠大脑后扣带回皮质区表达的影响,并探讨异丙酚预防或减轻氯胺酮所致精神症状及神经损害的机制。方法:雄性Wistar大鼠30只,随机分为生理盐水5ml组、氯胺酮100mg·kg-1组、异丙酚100mg·kg-1组、异丙酚50mg·kg-1+氯胺酮100mg·kg-1组、异丙酚100mg·kg-1+氯胺酮100mg·kg-1组。异丙酚与氯胺酮用药间隔15min。所用药物用生理盐水配至5ml经腹腔注射。各组动物于用药后2h,断头处死,分离脑组织,用半定量RTPCR技术和免疫组织化学方法检测各组cfosmRNA与cfos蛋白在大鼠后扣带回皮质区表达的变化。结果:氯胺酮可明显诱导cfosmRNA与cfos蛋白在大鼠后扣带回皮质区的表达;异丙酚自身不能诱导cfosmRNA和cfos蛋白的表达;预先给予异丙酚可显著抑制氯胺酮诱导的cfosmRNA和cfos蛋白在这一区域的表达,且抑制效应成剂量依赖性。结论:异丙酚可抑制氯胺酮诱导的cfosmRNA与cfos蛋白在大脑后扣带回皮质区的表达,这可能是其预防或减轻氯胺酮所致精神症状和神经损害的机制之一。AIM: To investigate the effects of propofol on ketamine-induced c-fos mRNA and protein expression in the rat posterior cingulate cortex,and to explore the possible mechanisms of using propofol to prevent or treat ketamine-induced psychotomimetic effects and neuronal damage.METHODS: Thirty male Wistar rats weighing 250-300 g were randomly divided into five groups with six animals in each:saline group which received normal saline 5 ml intraperitoneally ip (NS), ketamine 100 group which received ketamine 100 (mg·kg^(-1)) ip (K);propofol 100 group which received propofol 100 (mg·kg^(-1)) ip (P);propofol 50+ketmaine 100 group which received propofol 50 (mg·kg^(-1))+ketmaine 100 (mg·kg^(-1)) ip (P_1K) and propofol 100+Ketamine 100 group which received propofol 100 (mg·kg^(-1))+Ketamine 100 (mg·kg^(-1)) ip (P_2K).In group P_1K and P_2K, the interval between propofol and ketamine administration was 15 min.Two hours later,the animals were decapitated and brain was removed.c-fos mRNA expression in the posterion cingulate cortex was detected by semi-quantitative RT-PCR technique, c-fos protein expression in posterior cingulated cortex was determined by immuno-histochemical method.RESULTS: The levels of c-fos mRNA and c-fos protein expression were significantly different among 5 groups.Ketamine induced marked c-fos mRNA and c-fos protein expression in the posterior cingulate cortex.Propofol did not induce c-fos gene expression in this brain region.Propofol significantly inhibited ketamine-induced c-fos mRNA and c-fos protein expression in the posterior cingulated cortex in a dose-dependent manner.CONCLUSION: Propofol pretreatment can significantly inhibit ketamine-induced c-fos mRNA and protein expression in the posterior cingulate cortex.It may be one of mechanisms of inhibition of ketamine-induced psychotomimetic effect and neuronal damage by propofol.

关 键 词：异丙酚 氯胺酮 c—fos基因 大脑后扣带回皮质 

分 类 号：R971[医药卫生—药品]