腹腔注射催吐剂后非呕吐动物大鼠脑内呕吐反应区Fos阳性神经元的表达(英文)

Expression of Fos positive neurons in vomiting reflex regions of brain in nonvomiting rats after intraperitoneal injection of emetic

背景:给予猫类呕吐动物不同的催吐剂,发现孤束核、外侧被盖到腹外侧区这一弓形区域有大量Fos阳性神经元表达。并认为最后区、孤束核到腹外侧网状结构这一弓型区域是主要催吐部位。非呕吐动物注射催吐剂后是否会有相应反应。目的:观察腹腔注射催吐剂顺氯氨铂大鼠脑和脊髓内呕吐相关区域的Fos阳性神经元分布。设计:以动物为观察对象,随机对照实验。单位:河北师范大学生命科学学院的神经生理研究室和河北医科大学基础医学研究所生理室。材料:实验于2003-03/08在河北师范大学生命科学学院神经生理研究室,河北医科大学基础研究院生理室完成。选择雄性SD大鼠12只,体质量220～250g,清洁级。随机分为实验组6只,对照组6只。干预:实验组腹腔注射催吐剂顺氯氨铂10mg/kg,对照组注射等剂量的生理盐水后,于室温、安静、避光环境下观察大鼠的行为学变化。6h后取大鼠脑组织,进行冷冻连续切片,用免疫组织化学染色方法观察大鼠脑干和前脑核团的Fos阳性神经元的分布,并进行阳性细胞记数。主要观察指标:①注射催吐剂后大鼠的行为学观察。②大鼠脑内相关区域Fos阳性细胞数。结果:12只大鼠均进入结果分析。①两组大鼠在注射后20min内均为安静状态,蜷缩着趴卧,几乎无任何活动表现。注射后60min,对照组大鼠恢复正常,进食或饮水;而实验组大鼠处于蜷缩的趴卧状态,偶尔抬头或摆头,呼吸频率快且不均匀。注射后2h,实验组动物仍然腹部紧贴笼底趴卧,低头,鼻尖不规则晃动。5h后,实验组动物开始站立活动,呼吸正常,但仍不摄食或饮水。②在脑干的孤束核、最后区、外侧臂旁核和下丘脑的室旁核、视上核、弓状核的Fos阳性神经元[(64.3±9.6),(83.4±15.0),(148.8±19.9),(80.2±11.8),(20.7±3.8),(86.6±10.8)]明显高于对照组[(56.2±6.3),(73.5±9.9),(136.9±17.8),(66.1±10.3),(17.3±3.4),(78.8±10.5)]。结论:催吐剂能使大鼠产生内脏不适,其中枢神经系统内可能存在着与呕吐动物相似的催吐区,但可能缺乏与呕吐相关的调节机制。催吐剂的刺激使大鼠脑内相关区域Fos阳性神经元数量增加,提示非呕吐动物大鼠脑内也存在类似与恶心相关的神经化学通路。

BACKGROUND:It is discovered by administrating different emetics to vomiting animals,like cats,that there are a large amount of Fos positive neuronal expressions in the arc region from nucleus of solitary tract,lateral tegmentum to ventrolateral area.And it has been viewed that the arc region from area postrema, nucleus of solitary tract to ventrolateral reticular structure is the main emetic region.Whether do the nonvomiting animals reflect in response or not after emetic injection?OBJECTIVE:To observe the distribution of Fos positive neurons in relevant emetic regions of brain and spinal cord in rats after abdominal injection of emetic,cisplatin.DESIGN:Randomized controlled experiment based on animals.SETTING:Neural Physiological Research Room of Life Science College in Hebei Normal University and Physiological Room of Basic Medicine Institute in Hebei Medical University.MATERIALS:The experiment was performed in Neural Physiological Research Room of Life Science College in Hebei Normal University and Physiological Room of Basic Medicine Institute in Hebei Medical University from March to August 2003.Twelve SD male rats were employed,body weighted varied from 220 to 250 g,of cleangrade.They were randomized into experimental group of 6 rats and the control of 6 rats.INTERVENTIONS:In experimental group,the emetic,cisplatin,was injected abdominally 10 mg/kg.In the control,the physiological saline of same dose was injected.Afterwards,the activity changes in rats were observed at room temperature,quiet and lightavoided environment.Six hours later,the brain tissue was collected for frozen continuous sectioning.Immunohistochemical staining method was used to observe the distribution of Fos positive neurons in brainstem and forebrain nuclei and to count positive cell.MAIN OUTCOME MEASURES:①Behavior observation in rats after emetic injection.②Counts of Fos positive cell in relevant regions of brain in rats.RESULTS:Twelve rats all entered result analysis.①In 20 minutes after injection,the rats in both groups were in tranquilizing state,lying prone with body curled,almost without any movement.In 60 minutes after injection,the rats in the control were recovered to normal,free of eating or drinking.The rats in experimental group were in pronelying state with body curled.They rose up or shook the heads occasionally,and they breathed fast and uneven. In 2 hours after injection, in experimental group, the rats were still in abdominal prone tightly in the cage,with heads lowed and irregular shaking of noses.In 5 hours,the rats in experimental group began standing up and moving, with normal breathing, but they still did not eat or drink.②Fos positive neurons in solitary tract,area postrema and lateral parabrachial nucleus and paraventricular nucleus, supraoptic nucleus and arc nucleus in hypothalamus (64.3±9.6,83.4±15.0,148.8±19.9,80.2±11.8,20.7±3.8,86.6±10.8) were remarkably higher than those in the control(56.2±6.3,73.5±9.9,136.9±17.8,66.1±10.3,17.3±3.4,78.8±10.5).CONCLUSION:Emetics induce discomforts in internal organs of rats,due to which,there probably exist emetic regions similar to vomiting animals in central neural system.But it is probably lack of vomitingrelated adjusting mechanism.Emetics irritate the increase of Fos positive neurons in relevant regions in the brain of rat,which suggests that there exist relevant neural chemical pathways similar to nausea in the brain of nonvomiting rats.