CAJ | 학술논문

背景:阿片类药物多次用药可引起脑内有关神经部位出现形态及功能的适应性变化,这些适应性变化是导致药物渴求和戒断后复吸的重要神经生物学基础,但其确切的分子机制目前尚不清楚.目的:研究吗啡依赖形成及戒断对大鼠脑源性神经营养因子表达的影响,以期为脑源性神经营养因子参与阿片类药物依赖及戒断反应提供实验学依据.设计:以实验动物为观察对象的随机设计,对照研究.单位:一所医科大学医院的心理卫生中心.材料:实验于2004-03/2004-07在重庆医科大学药学系药理实验室完成.选择近交清洁级Sprague-Dawley大鼠30只,均为雄性,体质量200～250 g,购自解放军第三军医大学实验动物中心.按随机数字法将其分为空白对照组、吗啡依赖组、盐酸纳洛酮处理戒断组,每组10只.方法:采用剂量递增法皮下注射吗啡建立大鼠吗啡依赖模型,然后对戒断组大鼠皮下注射2 mg/kg的盐酸纳络酮激发戒断症状.空白对照组大鼠按同等剂量给予生理盐水.分别对建立模型的各组大鼠进行生物学和行为学的观察.应用免疫组化和地高辛标记寡核苷酸探针原位杂交技术检测3组大鼠不同脑区脑源性神经营养因子的表达水平.主要观察指标:①各组大鼠脑内脑源性神经营养因子蛋白、脑源性神经营养因子mRNA平均光密度的比较;②各组大鼠戒断症状评定比较.结果:吗啡依赖组大鼠前额叶皮层、蓝斑、海马脑源性神经营养因子蛋白的相对含量高于对照组(P＜0.05);吗啡依赖组大鼠前额叶皮层脑源性神经营养因子mRNA的相对含量高于对照组(P＜0.05).吗啡戒断组大鼠前额叶皮层、蓝斑、海马脑源性神经营养因子蛋白及其mRNA的相对含量均高于依赖组及对照组(P＜0.05).结论:慢性给予吗啡可影响大鼠相关脑区BDNF蛋白及其mRNA的表达,提示脑源性神经营养因子表达的改变参与吗啡依赖及戒断反应. 揹景:阿片類藥物多次用藥可引起腦內有關神經部位齣現形態及功能的適應性變化,這些適應性變化是導緻藥物渴求和戒斷後複吸的重要神經生物學基礎,但其確切的分子機製目前尚不清楚.目的:研究嗎啡依賴形成及戒斷對大鼠腦源性神經營養因子錶達的影響,以期為腦源性神經營養因子參與阿片類藥物依賴及戒斷反應提供實驗學依據.設計:以實驗動物為觀察對象的隨機設計,對照研究.單位:一所醫科大學醫院的心理衛生中心.材料:實驗于2004-03/2004-07在重慶醫科大學藥學繫藥理實驗室完成.選擇近交清潔級Sprague-Dawley大鼠30隻,均為雄性,體質量200～250 g,購自解放軍第三軍醫大學實驗動物中心.按隨機數字法將其分為空白對照組、嗎啡依賴組、鹽痠納洛酮處理戒斷組,每組10隻.方法:採用劑量遞增法皮下註射嗎啡建立大鼠嗎啡依賴模型,然後對戒斷組大鼠皮下註射2 mg/kg的鹽痠納絡酮激髮戒斷癥狀.空白對照組大鼠按同等劑量給予生理鹽水.分彆對建立模型的各組大鼠進行生物學和行為學的觀察.應用免疫組化和地高辛標記寡覈苷痠探針原位雜交技術檢測3組大鼠不同腦區腦源性神經營養因子的錶達水平.主要觀察指標:①各組大鼠腦內腦源性神經營養因子蛋白、腦源性神經營養因子mRNA平均光密度的比較;②各組大鼠戒斷癥狀評定比較.結果:嗎啡依賴組大鼠前額葉皮層、藍斑、海馬腦源性神經營養因子蛋白的相對含量高于對照組(P＜0.05);嗎啡依賴組大鼠前額葉皮層腦源性神經營養因子mRNA的相對含量高于對照組(P＜0.05).嗎啡戒斷組大鼠前額葉皮層、藍斑、海馬腦源性神經營養因子蛋白及其mRNA的相對含量均高于依賴組及對照組(P＜0.05).結論:慢性給予嗎啡可影響大鼠相關腦區BDNF蛋白及其mRNA的錶達,提示腦源性神經營養因子錶達的改變參與嗎啡依賴及戒斷反應.
배경:아편류약물다차용약가인기뇌내유관신경부위출현형태급공능적괄응성변화,저사괄응성변화시도치약물갈구화계단후복흡적중요신경생물학기출,단기학절적분자궤제목전상불청초.목적:연구마배의뢰형성급계단대대서뇌원성신경영양인자표체적영향,이기위뇌원성신경영양인자삼여아편류약물의뢰급계단반응제공실험학의거.설계:이실험동물위관찰대상적수궤설계,대조연구.단위:일소의과대학의원적심리위생중심.재료:실험우2004-03/2004-07재중경의과대학약학계약리실험실완성.선택근교청길급Sprague-Dawley대서30지,균위웅성,체질량200～250 g,구자해방군제삼군의대학실험동물중심.안수궤수자법장기분위공백대조조、마배의뢰조、염산납락동처리계단조,매조10지.방법:채용제량체증법피하주사마배건립대서마배의뢰모형,연후대계단조대서피하주사2 mg/kg적염산납락동격발계단증상.공백대조조대서안동등제량급여생리염수.분별대건립모형적각조대서진행생물학화행위학적관찰.응용면역조화화지고신표기과핵감산탐침원위잡교기술검측3조대서불동뇌구뇌원성신경영양인자적표체수평.주요관찰지표:①각조대서뇌내뇌원성신경영양인자단백、뇌원성신경영양인자mRNA평균광밀도적비교;②각조대서계단증상평정비교.결과:마배의뢰조대서전액협피층、람반、해마뇌원성신경영양인자단백적상대함량고우대조조(P＜0.05);마배의뢰조대서전액협피층뇌원성신경영양인자mRNA적상대함량고우대조조(P＜0.05).마배계단조대서전액협피층、람반、해마뇌원성신경영양인자단백급기mRNA적상대함량균고우의뢰조급대조조(P＜0.05).결론:만성급여마배가영향대서상관뇌구BDNF단백급기mRNA적표체,제시뇌원성신경영양인자표체적개변삼여마배의뢰급계단반응.
BACKGROUND: Multiple applications of opium medicines can induce the accommodative changes of morphology and function in some intracerebral nerve positions. These accommodative changes are important neurobiological bases inducing drug-desire and re-addiction after detoxification. However, the actual molecular mechanism is unclear at present.OBJECTIVE: To investigate the impacts of the generation of heroin-dependence and detoxification on brain-derived neurotrophic factor (BDNF) in rat to provide a laboratorial gist for the participation of BDNS in heroin-dependence and detoxification.DESIGN: A randomized controlled study by employing experimental animals as subjectsSETTING: Mental health center of a medical university affiliated hospital MATERIALS: The study was conducted in the Laboratory of Pharmacology,Faculty of Pharmacology, Chongqing Medical University between March 2004and July 2004. Totally 30 inbreeding clean male SD rats with a bodymass between 200 g and 250 g were obtained from the Experimental Animal Center of the Third Military Medical University of Chinese PLA. Rats were randomly divided into blank control group(control group), heroin-dependent group (heroin group), and naloxone detoxification group(naloxone group) with 10rats each.METHODS: Morphine was subcutaneously injected into the rat with dose-increasing method to establish heroin-dependence rat model. Rats of naloxone group received subcutaneously injection of 2 mg/kg of naloxone to excite abstinent symptoms. The same dose of normal saline (NS) was injected in rats of control group. Model rats of each group were observed biologically and behaviorally. BDNF expression at different brain zone of rats in three different groups was tested with immunohistochemistry and digoxin-labeled oligonucleoide probe in situ hybridization technique.Comparison of the evaluation of abstinent symptoms in rats of each group.RESULTS: In the heroin group, the relative content of BDNF protein was higher in frontal lobe cortex, locus caeruleus and hippocampus than that of the control group( P ＜ 0.05); BDNFmRNA relative content was higher in frontal lobe cortex than that of the control group( P ＜ 0. 05) . In naloxone group, BDNF and its mRNA relative contents in frontal lobe cortex, locus caeruleus and hippocampus were higher than that of heroin group and control group ( P ＜ 0.05 ).CONCLUSION: Chronic administration of heroin could affect BDNF protein and its mRNA expressions in the corresponding brain areas of the rats, which suggests that the change of BDNF expression participates in heroin-dependence and detoxification.