帕金森病大鼠模型的建立及MRI分析

Establishment and MRI analysis of rat modei of Parkinson's disease

目的:从行为学和MRI表现上评价6-OHDA分别毁损大鼠黑质及纹状体制备的偏侧帕金森病模型。方法:40只Wistar雄性大鼠随机分为3组:黑质毁损组20只,纹状体毁损组18只,假手术组2只。应用立体定向仪,分别作单点黑质毁损与两点纹状体毁损术。观察术后不同时期阿朴吗啡诱导的大鼠旋转行为,并进一步用高场强MRI活体检测帕金森病大鼠黑质、纹状体的毁损情况。结果:黑质毁损后第2周内有7只大鼠诱发出明显的旋转行为,且旋转次数>7转/min,模型成功率为35％。纹状体毁损后第2周有11只大鼠诱发出旋转行为,旋转次数<4转/min,第3周内旋转次数<5转/min,至术后第5周达到7转/min以上并保持稳定,模型成功率为61.1％。MRI显示:模型大鼠第3周内毁损侧黑质和纹状体较对侧出现了明显的MRI低信号区,且随着时间的延长低信号区逐渐减小,至第5周已基本消失。结论:应用6-OHDA小剂量两点毁损纹状体制备的偏侧帕金森病大鼠模型更加符合临床帕金森病病人的病程进展并具有较高的成功率,是帕金森病研究较为理想的模型。MRI扫描可以活体连续观察帕金森病大鼠模型的毁损情况,是客观评价和检测帕金森病大鼠模型的一种有效工具。

Objective: To evaluate rat modei of Parkinson's disease (PD) induced by unilateral nigral lesion or striatum lesion with 6-hydroxydopamine (6-OHDA) using behavior and MRI manifestation. Methods: 40 male Wistar rats were allotted into 3 groups randomly. The substantia nigra-lesioned group had 20 rats, with 18 in the striatum-lesioned group and 2 in pseudosurgery group. We stereotaxically impaired the substantia nigra in l point and striatum in 2 points and observed the rolling of rat induced by apomorphine in different stage, further examined the lesions of substantia nigra and striatum of PD rats in vivo under MRI. Results: 7 rats were induced to show obviously rolling behavior at the 2nd week after lesion of substantia nigra (>7 rolls/min). The success ratio of PD modei was 35%. While in striatum-lesioned group, 11 rats rolled at the 2nd week with rolling rate less than 4 rolls/min. The rolling rate was less than 5 rolls/min at the 3rd week, and more than 7 rolls/min after the 5th week and remaining stable. The success ratio of PD modei was 61.1%. The lesioned substantia nigra and striatum of PD rats showed obviously low MRI signal. The low signal regions shrank in correspondence with the time extended, and disappeared at the end of the 5th week. Conclusions: The PD rat modei gotten from bi-point lesions of striatum by small dose of 6-OHDA is more effective according to the clinical progress of PD patients with a higher success rate. It's a perfect modei to study PD. MRI scanning can be used to observe the lesions of PD rat modei in vivo continually, which is an available means to evaluate and examine the PD rat modei objectively.