吗啡依赖大鼠脑超微结构及其Bcl-2表达研究  

THE NEURONAL ULTRASTRUCTURE AND THE EXPRESSION OF BCL-2 IN SPRAGUEDAWLEY RATS BRAIN WITH MORPHINE DEPENDENCE

作　　者：胡华[1] 余会平[2] 蒙华庆[1] 罗庆华[1] 傅一笑[1] 冯坤[1] 高玉锋[1] 

机构地区：[1]重庆医科大学附属第一医院精神科,重庆400016 [2]四川省乐山市人民医院神经内科

出　　处：《现代预防医学》2010年第16期3114-3117,共4页Modern Preventive Medicine

基　　金：重庆市自然科学基金(渝科发计字:[2004]54号99;合同号8546)

摘　　要：[目的]明确吗啡依赖对大鼠不同脑区神经元超微结构及Bcl-2表达的影响。[方法]将Sprague-Dawley雄性大鼠随机分为吗啡依赖组、吗啡戒断组和空白对照组。采用递增法皮下注射吗啡建立大鼠吗啡依赖模型,等量注射生理盐水建立空白对照组。用H600透射电镜分别观察吗啡依赖组和空白对照组大鼠中脑腹侧背盖区(VTA)和蓝斑区(LC)神经元超微结构;用免疫组化和地高辛标记寡核苷酸探针原位杂交技术分别检测两组大鼠VTA、LC区Bcl-2蛋白及其mRNA的表达情况。[结果]与对照组比较,吗啡依赖组大鼠VTA、LC区神经元均出现髓样变性;吗啡依赖组大鼠VTA和LC的Bcl-2蛋白及其mRNA表达水平均较空白对照组低,其差异具有统计学意义(P﹤0.05)。[结论]吗啡依赖可导致大鼠VTA和LC神经元超微结构受损;吗啡依赖可能通过下调抑凋亡因子Bcl-2的表达,促进上述脑区神经元凋亡形成;Bcl-2蛋白表达及其mRNA水平降低可能是吗啡依赖致神经元超微结构损伤的重要环节之一。[Objective] To investigate the changes of ultrastructure and the expression of Bcl-2 in cerebral regions related to morphine dependence in Sprague-Dawley（SD） Rats Brain. [Methods] SD rats of male sex weighing 200-250g were randomly divided into 3 groups： Group I /chronic morphine dependence,GroupⅡ /morphine withdrawal and GroupⅢ /control. The chronic morphine dependence was induced by subcutaneous injections of increasing doses of morphine from 10 to 80 mg /kg for 5 consecutive days. The chronic morphine abstinence was induced by naloxone 2mg /kg after last dose of morphine.The control group was administered similar volume of normal saline. The ultrastructural changes of the ventral tegmental area and locus coeruleus area of the morphine dependence and control groups were observed respectively by transmission electron microscope H600. The expression of Bcl-2 and the levels of mRNA in ventral tegmental area（VTA） and locus coeruleus（LC） were assayed by immunohistochemistry and by digacin-labelled Bcl-2 cDNA probe by In Situ Hybridization respectively. [Results] Comparing to the control,the neuronal nucleus of locus coeruleus area in morphine dependent group was irregular and swelling,there are vesiculations and dissolve of nuclear matrix in the nucleus of LC neuron. Myelinic degeneration of neuronal fibra were observed in nerve cell and neurogliocyte of VTA;The levels of Bcl-2 and their mRNA in locus coeruleus and ventral tegmental area significantly decreased when compared with that in control rats after chronic administration of morphine（P ﹤ 0.05） . [Conclusion] Morphine dependence can induce the ultrastructure injury in ventral tegmental and locus coeruleus area of the rats by down-regulation of the anti-apoptotic Bcl-2 oncoprotein in rat brain;Morphine dependence can promote apoptosis of the neural cell in above cerebral regions related to morphine;The reduction of expression of Bcl-2 mRNA and their protein in the rat brain may explain the cause the ultrastructure injury.

关 键 词：吗啡 依赖 超微结构 BCL-2 

分 类 号：R542.2[医药卫生—心血管疾病]