蛋白酶体抑制剂诱导大鼠帕金森病模型的建立  

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

作　　者：汪纯[1] 马石楠[2] 杨棋[2] 王洋[2] 戢翰升[1] 

机构地区：[1]湖北医药学院附属十堰市人民医院神经外科,442000 [2]湖北医药学院附属太和医院神经外科,湖北十堰442000

出　　处：《重庆医学》2011年第29期2949-2951,F0003,共4页Chongqing medicine

摘　　要：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。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（P0.01） 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.

关 键 词：帕金森病 大鼠 蛋白酶体抑制剂 

分 类 号：R742.5[医药卫生—神经病学与精神病学]