奥氮平通过组胺H1兴奋弓状核神经元放电增加大鼠摄食量和体重

发布时间：2018-06-16 07:45

本文选题：奥氮平 + 倍他司汀　；参考：《新乡医学院》2015年硕士论文

【摘要】：背景奥氮平是一种新型抗精神病药物,能改善脑内多种神经通路的功能,因其副作用较少,安全性高,锥体外系不良反应小,目前已成为治疗精神分裂症和其他精神病性障碍的一线药物,但是奥氮平会出现代谢障碍性疾病特别是体重增加和肥胖,也引起临床上的关注。下丘脑弓状核位于下丘脑结节区室周带,参与垂体功能、摄食、自主神经活动、镇痛、内分泌等生理活动的调节。为明确奥氮平引起体重增加的副作用是否与弓状核神经元功能相关、是否与组胺H1受体相关,我们设计并完成了本实验。目的本文运用成年雌性SD大鼠为研究对象,通过给予药物干预,探讨奥氮平对大鼠体重的影响和弓状核神经元放电的作用,及组胺H1受体在这一作用中的机制。方法1.SD大鼠48只随机分为正常对照组(简称对照组,n=12)及模型组(n=36),给予高热量饮食1周,模型组再随机分为三组,每组12只,分别为：奥氮平治疗组(简称0组,1mg/kg, tid)、倍他司汀治疗组(简称B组,2.67mg/kg, tid)及奥氮平+倍他司汀治疗组(简称0+B)。2.药物干预2周,0组给予1mg/kg的奥氮平灌胃,B组给予2.67mg/kg倍他司汀灌胃,O+B组同时给予相同剂量奥氮平和倍他司汀,对照组不干预。3.记录各组大鼠的摄食量和体重增加量。4.采用旷场实验测其活动度；完成所有实验后,各组大鼠断头取脑,采用免疫组织化学技术检测各组大鼠弓状核神经元组胺H1受体蛋白表达；制备含弓状核的下丘脑离体脑片,采用细胞外记录法记录弓状核神经元放电。结果1.奥氮平治疗组大鼠体重显著增加,奥氮平+倍他司汀治疗组(0+B)大鼠体重介于奥氮平组和对照组之间,三组间大鼠体重有统计学意义。倍他司汀治疗组与正常对照组间差异没有统计学意义。2.旷场实验测试结果：奥氮平组对照组、与奥氮平+倍他司汀组间水平移动距离、竖立次数项目差异有统计学意义,倍他司汀治疗组与正常对照组间差异没有统计学意义。本组实验结果证明本实验所用剂量达到临床治疗有效浓度。3.电生理结果：奥氮平组弓状核神经元放电频率、幅度均高于对照组、奥氮平+倍他司汀组,奥氮平+倍他司汀组高于对照组,倍他司汀组低于正常对照组。4.免疫组织化学检测结果显示：奥氮平组与对照组、倍他司汀组弓状核神经元组胺H1受体蛋白表达之间有统计学意义；奥氮平+倍他司汀治疗组与正常对照组间差异没有统计学意义。结论1.奥氮平能增加大鼠的摄食量和体重,该作用与奥氮平通过组胺H1受体途径增强大鼠下丘脑弓状核神经元放电有关。2.倍他司汀部分阻断奥氮平对大鼠的摄食量和体重、下丘脑弓状核神经元放电,提示组胺H1受体是奥氮平增强弓状核神经元的作用途径之一
[Abstract]:Background olanzapine is a novel antipsychotic drug that can improve the function of multiple neural pathways in the brain because of its less side effects, higher safety and less adverse reactions to extrapyramidal system. Currently, it has become a first-line drug for the treatment of schizophrenia and other psychiatric disorders, but olanzapine may lead to metabolic disorders, especially weight gain and obesity, which has also aroused clinical concern. The hypothalamic arcuate nucleus is located in the periventricular zone of hypothalamic tuberculous area, and participates in the regulation of pituitary function, feeding, autonomic nervous activity, analgesia, endocrine and other physiological activities. To determine whether the side effects of olanzapine on weight gain are related to the function of neurons in arcuate nucleus and histamine H1 receptor, we designed and completed this experiment. Objective to investigate the effect of olanzapine on body weight and the firing of arcuate nucleus neurons and the mechanism of histamine H 1 receptor in adult female SD rats. Methods 1. Forty-eight SD rats were randomly divided into normal control group (control group, n = 12) and model group, which were given a high-calorie diet for one week. The model group was randomly divided into three groups, 12 rats in each group. The results were as follows: olanzapine treatment group (0 group): 1 mg / kg, tidd, betaxime group (B group, 2.67 mg / kg, tid) and olanzapine betaprostatin treatment group (0 BX. 2). Two weeks after drug intervention, group B was given the same dose of olanzapine and betastatin by intragastric administration of 2.67mg/kg betastine, but the control group was not treated with oranzapine or betastatin, while the control group was not treated with oranzapine or betastatin. Food intake and weight gain of rats in each group were recorded. 4. 4. After all the experiments, the rats in each group had their heads cut off, their brains were removed, the expression of histamine H1 receptor protein in neurons of the arcuate nucleus of each group was detected by immunohistochemical technique, and the isolated hypothalamus slices containing arcuate nucleus were prepared. The arcuate nucleus neurons were recorded by extracellular recording. Result 1. The weight of rats in olanzapine treatment group was significantly increased, and the weight of olanzapine group was between the control group and the olanzapine group, and the weight of the three groups was significantly higher than that of the control group. There was no significant difference between betastatin treatment group and normal control group. 2. 2. The results of open field test showed that there were significant differences in horizontal moving distance and erecting times between the control group and the olanzapine group, but there was no significant difference between the betastatin treatment group and the normal control group. The results of this experiment proved that the dose used in this experiment reached the effective concentration of clinical treatment. Electrophysiological results: the firing frequency and amplitude of arcuate nucleus neurons in olanzapine group were higher than those in control group, and those in olanzapine group were higher than those in control group, and those in betastatin group were lower than those in normal control group. The expression of histamine H1 receptor protein in arcuate nucleus neurons in olanzapine group was significantly different from that in control group and betastatin group. There was no significant difference between olanzapine and normal control group. Conclusion 1. Olanzapine can increase the intake and body weight of rats, which is related to the effect of olanzapine through histamine H _ 1 receptor pathway to enhance the hypothalamic arcuate nucleus neurons discharge. Betahistine partially blocked the intake and body weight of olanzapine and the discharges of arcuate nucleus neurons in hypothalamus, suggesting that histamine H 1 receptor is one of the mechanisms of olanzapine in enhancing arcuate nucleus neurons.
【学位授予单位】：新乡医学院
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R749.3

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