【摘 要】
：
目的：利用斑马鱼这一新型模式动物建立行为模型,考察成瘾性药物甲基苯丙胺(METH)对于斑马鱼成鱼游泳行为的影响及谷氨酸转运体表达量的变化.方法：利用Zebralab 斑马鱼行为视频跟踪分析系统自动记录动物行为参数,以运动路程、穿越次数及在顶部停留时间作为成鱼测试指标,甲基苯丙胺暴露浓度0.2～20 mg·L-1,分别急性暴露30min后进行60min 行为测试；之后利用实量定量PCR 考察成鱼全脑
【机 构】
：
军事医学科学院毒物药物研究所,北京 100850
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目的：利用斑马鱼这一新型模式动物建立行为模型,考察成瘾性药物甲基苯丙胺(METH)对于斑马鱼成鱼游泳行为的影响及谷氨酸转运体表达量的变化.方法：利用Zebralab 斑马鱼行为视频跟踪分析系统自动记录动物行为参数,以运动路程、穿越次数及在顶部停留时间作为成鱼测试指标,甲基苯丙胺暴露浓度0.2～20 mg·L-1,分别急性暴露30min后进行60min 行为测试；之后利用实量定量PCR 考察成鱼全脑中质膜型谷氨酸转运体(GLT1)和囊泡型谷氨酸转运体(VGLUT1～3)mRNA 表达量变化.结果：在所测试的浓度范围内,METH 急性暴露对斑马鱼的运动距离无显著性影响,而使斑马鱼垂直方向的穿越次数及在上半区停留时间呈非常显著的下降( P ＜ 0.01,与正常组相比),且这种降低与甲基苯丙胺有剂量依赖关系.在METH0.2～2 mg·L-1 范围内急性暴露可使斑马鱼成鱼脑glt1mRNA 水平呈剂量依赖性上调(2 mg·L－1 时P ＜0.001,与正常组相比),而在高剂量处理时,与正常组相比,glt1 水平有显著下调,提示GLT1 具有双向调节作用；METH 急性处理后,只有2mg·L-1 剂量下vglut1 显著上调( P ＜0.001),其他剂量组均无显著变化；而METH 可使vglut2 在最低剂量时显著下调,而后vglut2 水平逐渐回复,至最高剂量20mg·L-1时与正常组已无显著性差异；vglut3 在低剂量时无显著性变化,高剂量下显著上调,但无剂量关系.结论：建立了甲基苯丙胺致斑马鱼神经损伤模型,甲基苯丙胺对于斑马鱼行为产生特征性影响且具有剂量关系.急性甲基苯丙胺可造成神经损伤,并与谷氨酸转运体有密切关系,在甲基苯丙胺致斑马鱼神经损伤的机制中,GLT1 及VGLUT2 所起到的作用值得进一步研究.
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