【作者】 钱玲玲；

【导师】 朱永平；

【作者基本信息】 浙江大学 ， 卫生毒理学， 2011， 硕士

【摘要】 1目的：从神经元凋亡角度探讨吗啡依赖的可能机理,研究Glu-Con-G、Glu-Con-G[1-13]对吗啡躯体依赖的干预作用及可能机制。2方法：采用条件性位置偏爱(conditioned place preference,CPP)和躯体依赖模型,利用透射电子显微镜、免疫印迹法检测成瘾小鼠纹状体脑区神经元的凋亡情况及相关蛋白含量变化。3结果：1.吗啡诱导小鼠CPP建立和复燃阶段纹状体脑区神经元核固缩变形,染色质边集,CPP消退阶段神经元未出现显著异常,但有异常溶酶体出现。2.吗啡诱导小鼠CPP建立、消退和复燃阶段纹状体脑区神经元树突、轴突数量明显增多、密集。3.吗啡诱导小鼠CPP建立、消退和复燃阶段Procaspase3蛋白含量在Hp、PFC脑区无明显变化,但在纹状体脑区于CPP建立和复燃阶段含量减少。4.150、300、600pmol Glu-Con-G和Glu-Con-G[1-13]呈剂量-效应依赖性方式抑制吗啡成瘾小鼠戒断跳跃,150、300、600pmol Glu-Con-G和300、600 pmol Glu-Con-G[1-13]还能抑制小鼠体重减轻症状。5.150、300、600pmolGlu-Con-G和Glu-Con-G[1-13]均能显著上调吗啡成瘾小鼠纹状体脑区Procaspase3蛋白含量。4结论：1.多次吗啡处理,可导致小鼠纹状体脑区在CPP建立、复燃阶段出现异常凋亡,CPP消退阶段未见显著凋亡但有异常溶酶体出现。2.长期吗啡处理上调纹状体脑区神经元突触数量,树突、轴突密集,下调Procaspase3蛋白含量。3. Glu-Con-G和Glu-Con-G[1-13]能干预吗啡所致小鼠躯体依赖,并能上调纹状体脑区Procaspase3蛋白含量,且呈剂量相关性。更多还原

【Abstract】 1 Purpose:We approached the possible mechanism of morphine dependence from the perspective of neuronal apoptosis, then evaluated the intervention effect of Con-G and analogues on morphine physical dependence.2 Methods:After establishing morphine induced conditioned place preference and physical dependence model, transmission electron microscopy and western blotting were used to detect the apoptosis and the changes of the levels of related proteins.3 Results:1. In the CPP acquisition and reinstatement phases, striatal neurons karyopyknosis deformation, chromatin margination, the electron density increased. In the CPP extinction phase, striatal neurons appeared normal, uniform electron density; abnormal lysosome scattered.2. In the CPP acquisition, extinction and reinstatement phases, larger amounts and more intensive shaft-shaft synapses, the axon-dendrite synapses appeared in striatum.3. In the CPP acquisition, extinction and reinstatement phases, the relative protein levels of Procaspase3 were no difference between saline group mice and morphine mice in Hp and PFC. But in stratum, in the CPP acquisition and reinstatement phases, the relative protein levels of Procaspase3 decreased.4.150、300、600pmolGlu-Con-G and Glu-Con-G[1-13] can inhibit the naloxone-induced jumping behavior in a dose-effect dependent manner.150、300、600pmolGlu-Con-G and 150、600pmol Glu-Con-G[1-13] can inhibit the naloxone-induced body weight loss.5.150、300、600pmolGlu-Con-G and Glu-Con-G[1-13] significantly increased the level of Procaspase3 in striatum in morphine induced physical dependence mice.4 Conclusions:1. In the CPP acquisition phase, there was apoptosis in striatum brain region; in the CPP extinction phase, there were no significant abnormalities, but abnormal lysosome. In the CPP reinstatement phase, it appeared apoptosis.2. Long-term morphine treatment increased the number of synapses, dendrites, axons more intensive. It can also decrease the levels of Procaspase3.3. Glu-Con-G、Glu-Con-G[1-13] can inhibit morphine-induced mice physical dependence. They can also significantly increase the level of Procaspase3 in striatum.更多还原