摘要
目的探讨氯胺酮对大鼠前脑缺血-再灌注（I／R）后海马解偶联蛋白2（uncoupling proteins 2，UCP2）表达的影响及在脑保护作用中的机制。方法45只体质量在250～300g的雄性Wistar大鼠随机分为3组，每组15只。双侧颈总动脉夹闭加放血降压再回输法建立前脑缺血-再灌注模型，大鼠脑电图出现低幅持续性7 Hz、30～40μV的θ节律为脑缺血模型成功标志。对照组（C组）：仅暴露双侧颈总动脉，未放血降压及夹闭双侧颈总动脉；缺血损伤组（I组）：放血法使平均动脉压降到（40±5）mmHg时，夹闭双侧颈总动脉10min，侧脑室内注射生理盐水（1．0mg／kg）；氯胺酮干预组（K组）：放血降压、夹闭双侧颈总动脉与I组相同，侧脑室内注射氯胺酮（1．0mg／kg）。于再灌注6h后断头取脑组织，光镜下观察脑组织病理学改变；半定量逆转录-聚合酶链反应（RT-PCR）技术检测海马UCP2 mRNA表达（n=7）；免疫组织化学（IH）法检测海马UCP2蛋白表达（n=8）。RT-PCR、IH结果应用方差分析（ANOVA）进行统计学分析。结果与C组UCP2 mRNA（0．91±0．02）表达比较，I组脑I／R后6h UCP2 mRNA（1．06±0．02）和K组脑I／R后6h UCP2 mRNA（1．18±0．06）表达升高（P〈0．05），K组脑I／R后6h UCP2 mRNA表达高于I组（P〈0．05）；C组UCU2蛋白少量表达（17．91±5．49），I组脑I／R后6h UCP2蛋白（31．56±4．01）和K组脑I／R后6h UCP2蛋白（44．61±4．96）表达升高（P〈0．05），K组脑I／R后6h UCP2蛋白表达高于I组（P〈0．05）。结论氯胺酮促进大鼠前脑缺血-再灌注（I／R）后海马UCP 2mRNA和蛋白的表达，可能是其对脑缺血-再灌注损伤保护作用的机制之一。
Objective To investigate the effect of ketamine on hippocampal uncoupling protein 2 （UCP 2） expression after forebrain ischemia-reperfusion （I/R） in rats and the mechanism of protective effect of ketamine on brain. Method Forty-five male Wistar rats weighing 250 - 300 g were randomly divided into 3 groups, with 15 animals in each group. Forebrain I/R was established by occlusion of bilateral carotid artery combined with hypotension, EEG in a sustained low rate of 7 Hz, 30 - 40μV θ rhythm was the success signs of forebrain I/R. Control group （C） ：sham operation was performed; I/R group （I） ： bilateral common carotid arteries were clamped for 10 min combined with hypotension [MAP： （40 ± 5） mmHg] induced by exsanguinations, then saline （1 mg/kg） was injected into the lateral cerebral ventricle using microsyringe; ketamine group （K） ： ketamine （1 mg/kg） was injected into the lateral cerebral ventricle using microsyringe after I/R. The animals were decapitated, the brain was immediately removed, and the hippocampal tissues were dissociated at 6 h after reperfusion. The cerebral I/R injury was observed with light microscope, the levels of UCP 2 mRNA expression in hippocampus were detected by using semiuantitative RT-PCR technique （ n = 7）, coronal sections including hippocampal tissue were obtained for detection of UCP 2 protein expression by immuno-histochemistry （IH） method （n = 8）. The RT-PCR and IHdata were expressed as the mean ± SD, the statistical significance was determined by one-way ANOVA. Results The UCP 2 mRNA expression was （ 1.06 ± 0.02） in group I and （ 1.18 ±0.06）in group K increased significantly compared with that in group C（0.91 ± 0.02） （P 〈 0.05）, there were more UCP 2 mRNA expression in group K increased than that in group I （P 〈 0.05）. The expression of UCP 2 protein was （31.56±4.01） in group I and （44.61 ± 4.96） in group K, increased significantly compared with that in group C （17.91 ± 5.49） （P 〈
出处
《中华急诊医学杂志》
CAS
CSCD
2008年第10期1045-1049,共5页
Chinese Journal of Emergency Medicine
基金
国家自然科学基金资助项目（30240023）
黑龙江省留学归国基金资助项目（LC06C29）
中国博士后科学基金（2003034343）
关键词
氯胺酮
脑缺血
再灌注损伤
解偶联蛋白2
Ketamine
Cerebral ischemia
Reperfusion injury
Uncoupling protein 2
