【摘要】 目的:建立一种改进的帕金森病大鼠模型制作方法,并对模型进行综合评价。方法:实验于2004-02/2005-06在军事医学科学院干细胞研究中心完成。①选取Wistar大鼠60只,随机分为3组,传统组20只,改良组30只,对照组10只。②传统组向右侧中脑黑质致密部和中脑腹侧被盖区两点各注射6-羟基多巴胺8μg制作传统帕金森病大鼠模型,改良组向中脑腹侧被盖区单点6-羟基多巴胺12μg制作改良帕金森病大鼠模型。对照组向右侧中脑黑质致密部和中脑腹侧被盖区两点各注射含2g/L抗坏血酸的生理盐水4μL。③检测各组大鼠行为学变化及黑质多巴胺能神经元变化。结果:对照组和传统组术后分别有1只和4只动物在1周内死亡,改良组无动物死亡。行为学和免疫组化检测显示:①改良组30只大鼠有22只旋转稳定,平均转数>7r/min,成功率超过70%,与传统组相当。改良组大鼠死亡率低于传统组(20%)和对照组(10%)。②术后传统组和改良组均有部分动物出现震颤、活动迟缓、易激惹、竖毛、尾僵等异常行为。③成功帕金森病模型大鼠中脑黑质注射侧神经元数量明显减少,达90%以上,改良组与传统组比较差异无显著性(P>0.05),与对照组比较注射侧黑质多巴胺能神经元显著减少(P<0.001)。结论:改良帕金森病大鼠模型方法简便实用,动物死亡率低,模型成功率高,可以较快建立稳定的帕金森病大鼠模型。更多还原

【Abstract】 AIM To study an improved method to establish rat model of Parkinson disease and evaluate the model comprehensively. METHODS The experiment was carried out in the Research Center of Stem Cells Academy of Military Medical Sciences between February 2004 and June 2005. ① Sixty Wistar rats were randomly divided into traditional group n=20 improved group n=30 and control group n=10. ② The rats were administered with stereotaxic microinjection of 6-hydroxydopamine 6-OHDA into the right substantia nigra compact part and the midbrain ventral tegmental area in the traditional group and only the midbrain ventral tegmental area in the improved group and those in the control group were injected with 4 μL saline containing ascorbic acid 2 g/L into the right substantia nigra compact part and the midbrain ventral tegmental area. ③ The changes of behaviors and the quantity of midbrain nigra dopaminergic neurons were detected. RESULTS One and 4 rats died within 1 week postoperatively in the control group and traditional group respectively and there was no death in the improved group. Behavioral test and immunohistochemical detection showed that ① In the improved group n=30 22 rats rotated stably with an average > 7 rounds per minute and the successful ratio exceeded 70% which was equivalent to that in the traditional group. The mortality in the improved group was lower than that in the traditional group 20% and control group 10%. ② Postoperatively part of the rats in the traditional group and improved group had the abnormal behaviors of tremor retardation irritability piloerection and stiffness of tail etc. ③ The number of dopaminergic neurons in midbrain nigra of the injected side was obviously reduced by more than 90% in the successful rat models of Parkinson disease and there was no significant difference between the improved group and traditional group P > 0.05 which were significantly decreased as compared with that in the control group P < 0.001. CONCLUSION The improved method for Parkinson disease is convenient and practical with lower mortality of animal and higher successful rate of model establishment and stable rat models of Parkinson disease can be established more quickly.更多还原