蛋白酶体抑制剂诱导大鼠帕金森病模型的建立

目的探讨用蛋白酶体抑制剂乳胞素(lactacystin)建立帕金森病(PD)大鼠模型的方法,并对模型进行综合评价。方法 应用立体定向单针道双靶点方法在大鼠黑质致密部注射乳胞素,观察大鼠行为变化、黑质细胞形态及黑质致密部酪氨酸羟化酶的变化。结果 注射乳胞素1周后,大鼠出现活动迟缓、震颤、少动、头向健侧倾斜、竖毛等行为改变,阿扑吗啡诱导后出现向左旋转;给药后4周,每组大鼠运动活跃性均低于生理盐水组。病理学检查发现进针部位均有小胶质细胞增生、多巴胺能神经元胞体肿胀或萎缩;8μg组变化较明显,部分黑质细胞内出现嗜伊红包涵体;2、4、8μg组的酪氨酸羟化酶(TH)免疫阳性细胞数与生理盐水组相比差异有统计学意义(P<0.01),随着注射剂量的提高TH免疫阳性细胞数逐渐减少。结论 采用单针道双靶点注射Lactacystin能成功建立临床症状和病理特征均符合PD要求的大鼠模型。

Establish of Parkinsons's disease model induced by lactacystin in rats

Objective To establish one model of Parkinson′s disease(PD)for rats,and to comprehensively evaluate the model.Methods The rat PD model was established by the unilateral single-path and two-targets injection of lactacystin into the NSr through stereotaxic technique.And then,the behaviors features,the tyrosine hydroxylase-immunoreactivity in substantia nigra were observed.Results After lactacystin injection for 1 week,the behavior of rats was changed,including progressively bradykinetic,contralateral head tilting and tremor,and apomorphine-induced contralateral behavior was observed.After 4 weeks,sports activity of rats in each group were reduced compared with the saline group.Pathological examination revealed microglia proliferation and dopaminergic neurons swelling or shrinking in the needle parts;The change in 8 μg group was more apparent,and some of nigral cells in it contained Lewy body.The number of tyrosine hydroxylase positive cells in 2 μg,4 μg and 8 μg groups were significantly decreased(P<0.01) compared with the control group.And as the dose increased the number of TH immunoreactive cells gradually decreased.Conclusion The rat PD model established by the unilateral single-path and two-targets injection of lactacystin into the NSr through stereotaxic technique is similar to the clinical PD both in symptoms and pathological changes.