本文選題：奧氮平 + 倍他司汀��； 參考：《新鄉(xiāng)醫(yī)學(xué)院》2015年碩士論文

【摘要】：背景奧氮平是一種新型抗精神病藥物,能改善腦內(nèi)多種神經(jīng)通路的功能,因其副作用較少,安全性高,錐體外系不良反應(yīng)小,目前已成為治療精神分裂癥和其他精神病性障礙的一線藥物,但是奧氮平會出現(xiàn)代謝障礙性疾病特別是體重增加和肥胖,也引起臨床上的關(guān)注。下丘腦弓狀核位于下丘腦結(jié)節(jié)區(qū)室周帶,參與垂體功能、攝食、自主神經(jīng)活動、鎮(zhèn)痛、內(nèi)分泌等生理活動的調(diào)節(jié)。為明確奧氮平引起體重增加的副作用是否與弓狀核神經(jīng)元功能相關(guān)、是否與組胺H1受體相關(guān),我們設(shè)計(jì)并完成了本實(shí)驗(yàn)。目的本文運(yùn)用成年雌性SD大鼠為研究對象,通過給予藥物干預(yù),探討奧氮平對大鼠體重的影響和弓狀核神經(jīng)元放電的作用,及組胺H1受體在這一作用中的機(jī)制。方法1.SD大鼠48只隨機(jī)分為正常對照組(簡稱對照組,n=12)及模型組(n=36),給予高熱量飲食1周,模型組再隨機(jī)分為三組,每組12只,分別為：奧氮平治療組(簡稱0組,1mg/kg, tid)、倍他司汀治療組(簡稱B組,2.67mg/kg, tid)及奧氮平+倍他司汀治療組(簡稱0+B)。2.藥物干預(yù)2周,0組給予1mg/kg的奧氮平灌胃,B組給予2.67mg/kg倍他司汀灌胃,O+B組同時給予相同劑量奧氮平和倍他司汀,對照組不干預(yù)。3.記錄各組大鼠的攝食量和體重增加量。4.采用曠場實(shí)驗(yàn)測其活動度；完成所有實(shí)驗(yàn)后,各組大鼠斷頭取腦,采用免疫組織化學(xué)技術(shù)檢測各組大鼠弓狀核神經(jīng)元組胺H1受體蛋白表達(dá)；制備含弓狀核的下丘腦離體腦片,采用細(xì)胞外記錄法記錄弓狀核神經(jīng)元放電。結(jié)果1.奧氮平治療組大鼠體重顯著增加,奧氮平+倍他司汀治療組(0+B)大鼠體重介于奧氮平組和對照組之間,三組間大鼠體重有統(tǒng)計(jì)學(xué)意義。倍他司汀治療組與正常對照組間差異沒有統(tǒng)計(jì)學(xué)意義。2.曠場實(shí)驗(yàn)測試結(jié)果：奧氮平組對照組、與奧氮平+倍他司汀組間水平移動距離、豎立次數(shù)項(xiàng)目差異有統(tǒng)計(jì)學(xué)意義,倍他司汀治療組與正常對照組間差異沒有統(tǒng)計(jì)學(xué)意義。本組實(shí)驗(yàn)結(jié)果證明本實(shí)驗(yàn)所用劑量達(dá)到臨床治療有效濃度。3.電生理結(jié)果：奧氮平組弓狀核神經(jīng)元放電頻率、幅度均高于對照組、奧氮平+倍他司汀組,奧氮平+倍他司汀組高于對照組,倍他司汀組低于正常對照組。4.免疫組織化學(xué)檢測結(jié)果顯示：奧氮平組與對照組、倍他司汀組弓狀核神經(jīng)元組胺H1受體蛋白表達(dá)之間有統(tǒng)計(jì)學(xué)意義；奧氮平+倍他司汀治療組與正常對照組間差異沒有統(tǒng)計(jì)學(xué)意義。結(jié)論1.奧氮平能增加大鼠的攝食量和體重,該作用與奧氮平通過組胺H1受體途徑增強(qiáng)大鼠下丘腦弓狀核神經(jīng)元放電有關(guān)。2.倍他司汀部分阻斷奧氮平對大鼠的攝食量和體重、下丘腦弓狀核神經(jīng)元放電,提示組胺H1受體是奧氮平增強(qiáng)弓狀核神經(jīng)元的作用途徑之一
[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.
【學(xué)位授予單位】：新鄉(xiāng)醫(yī)學(xué)院
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2015
【分類號】：R749.3

【參考文獻(xiàn)】

相關(guān)期刊論文 前3條

1 劉廣益，方一心，，曾志源;下丘腦弓狀核的形態(tài)結(jié)構(gòu)與生理功能[J];四川解剖學(xué)雜志;1996年03期

2 王彬;胡峻梅;李寶花;張校明;;氟西汀合并奧氮平治療難治性抑郁癥對照研究[J];山東精神醫(yī)學(xué);2006年02期

3 康冬梅;趙翠平;姚慧;黃大可;葉山東;;胃和弓狀核中obestatin在攝食行為調(diào)節(jié)中的作用[J];安徽醫(yī)科大學(xué)學(xué)報;2012年05期

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