摘要
目的探索通过脑室内注射蛋白酶体抑制剂乳胞素的方法建立帕金森病(PD)食蟹猴动物模型。方法选取老龄健康雄性食蟹猴3只,随机分为实验猴2只(A猴、B猴)、对照猴1只(C猴)。实验猴多次重复脑室内注射乳胞素,对照猴注射同等剂量的0.9%氯化钠溶液。于给药前后60 min观察其行为学变化。采用免疫组织化学方法染色和行为学评分对模型进行验证。结果行为学观察结果示,实验猴出现类似PD典型的手臂震颤、运动迟缓、运动量减少等行为学改变;行为学评分与对照猴相比,差异有统计学意义(P<0.05)。免疫组化结果示,实验猴酪氨酸羟化酶(TH)阳性面积较对照猴减少,差异有统计学意义(P<0.05);实验猴平均吸光度较对照猴减少,差异有统计学意义(P<0.05)。实验猴α-突触核蛋白(α-syn)阳性面积较对照猴增加,差异有统计学意义(P<0.05);实验猴平均吸光度较对照猴增加,差异有统计学意义(P<0.05)。结论该实验采用小剂量、多次重复脑室内注射蛋白酶体抑制剂乳胞素方式产生了类似PD的行为学改变,免疫组化结果显示黑质存在PD样病变,可认为已建立食蟹猴慢性PD模型,该模型能够较好地模拟PD患者的临床症状和病理进程。
Objective To establish a cynomolgus monkey model of Parkinson’s disease(PD)through intracerebroven⁃tricular injection of the proteasome inhibitor lactacystin.Methods Three elderly healthy male cynomolgus monkeys were randomly divided into experimental group,control group,and blank control group,with one cynomolgus monkey in each group.The experimental monkey was given repeated intracerebroventricular injection of lactacystin,the control monkey was given the injection of an equal dose of 0.9%sodium chloride solution,and the blank control monkey was not given any treat⁃ment.Behavioral changes were observed at 60 minutes before and after administration.Immunohistochemical staining and behavioral score were used to validate the model.Results Behavioral observation showed that the experimental monkey had the typical behavioral changes of PD such as arm tremor,bradykinesia,and reduced amount of exercise,and there was a significant difference in behavioral score between the experimental monkey and the control monkey(P<0.05).Immunohis⁃tochemistry showed that compared with the blank control monkey,the experimental monkey and the control monkey had a significant reduction in TH-positive area,and compared with the control monkey,the experimental monkey had significant reductions in TH-positive area(P<0.05)and mean absorbance(P<0.05).Compared with the blank control monkey,the ex⁃perimental monkey and the control monkey had a significant increase inα-synuclein(α-syn)-positive area,and theα-syn-positive area in the experimental monkey was 214.5%that in the control monkey(P<0.05);the experimental monkey had a significant increase in mean absorbance compared with the control monkey(P<0.05).Conclusions In this experiment,re⁃peated small-dose intraventricular injection of the proteasome inhibitor lactacystin produced the behavioral changes similar to those in PD,and immunohistochemical results showed PD-like lesions in the substantia nigra;therefore,a cynomolgus monkey model of chronic PD can be considered successfully established.This model can better simulate the clinical symp⁃toms and pathological process of PD patients and is thus a reliable experimental animal model for studying the etiology,pathogenesis,drug therapy,and gene therapy for PD.
作者
宋净洋
郭清华
车祥源
郑志勇
彭俊宇
邢红霞
刘捷
SONG Jing-Yang;GUO Qing-Hua;CHE Xiang-Yuan;ZHENG Zhi-Yong;PENG Jun-Yu;XING Hong-Xia;LIU Jie(The Third Affiliated Hospital of Xinxiang Medical College,Xinxiang,Henan 453000;China 2.The First Affiliated Hospital of Xinxiang Medical College,Xinxiang,Henan 453100;China 3.Icordgraduate School,University of Brithish Columbia,Vancouver,British ColumbiaV5Z 1M9,Canada)
出处
《国际神经病学神经外科学杂志》
2021年第4期321-326,共6页
Journal of International Neurology and Neurosurgery
基金
河南省科技攻关项目基金(182102310156)。
