百草枯诱导帕金森病小鼠行为学和病理学变化的动态观察  

Dynamic observation of behavior and histopathology in mice with paraquat-induced Parkinson’s disease

作　　者：王永玲 郑晶[2] 张晓峰 WANG Yong-ling;ZHENG Jing;ZHANG Xiao-feng(Department of Health Toxicology,Public Health School,Harbin Medical University,Harbin,Heilongjiang 150081,China;不详)

机构地区：[1]哈尔滨医科大学公共卫生学院卫生毒理学教研室,黑龙江哈尔滨150081 [2]黑龙江省疾病预防控制中心公共卫生监测所,黑龙江哈尔滨150030

出　　处：《现代预防医学》2020年第22期4160-4163,4167,共5页Modern Preventive Medicine

基　　金：哈尔滨医科大学于维汉院士杰出青年培养基金。

摘　　要：目的动态观察百草枯(PQ)诱导帕金森病(PD)模型过程中小鼠行为学及黑质组织病理学变化。方法雄性C57BL/6小鼠腹腔注射PQ(10 mg/kg),每周2次,连续6周。每周末次染毒后24 h,通过旷场实验、步态分析实验和抓力实验检测小鼠行为学变化,并进行中脑黑质组织病理学观察。结果模型建立过程中,模型组和对照组小鼠体重没有明显变化。与相同时间点对照组比较,旷场实验从第3周开始,模型组小鼠直立探究次数和总运动路程减少,差异有统计学意义(t=3.03、2.41、3.71、3.05,P<0.05;t=3.08、2.30、2.94、2.33,P<0.05);步态分析实验从第5周开始,模型组小鼠步宽增加和步长减小,差异均有统计学意义(t=2.46、2.35,P<0.05;t=2.17、3.35,P<0.05);抓力实验表明从第3周开始,模型组小鼠抓力明显降低,差异有统计学意义(t=2.19、2.51、2.81、3.32,P<0.05)。中脑黒质组织病理学观察发现从第3周开始,模型组小鼠中脑黑质出现进行性的胶质细胞聚集及神经元胞核固缩、变性和死亡,神经元数量减少。结论腹腔注射PQ诱导PD模型,从第3周开始小鼠逐渐出现类PD样特征性改变,且黑质组织的胶质细胞活化可能早于神经元的变性死亡。Objective To observe dynamically the changes of behavior and histopathology in model mice with Parkinson’s disease(PD)induced by paraquat(PQ).Methods Male C57 BL/6 mice were intraperitoneally injected with PQ(10 mg/kg),twice a week for 6 consecutive weeks.The behavioral changes of the mice were detected by open field test,gait analysis test and grasp test after 24 hours of last exposure each week.Then histopathological changes of substantia nigra were observed.Results There was no significant difference of body weight between the model group and the control group during PQ exposure.Compared with the control group at the same time point,the open field test showed that the number of upright inquiry and the total exercise distance decreased significantly(t=3.03,2.41,3.71,3.05;P<0.05;t=3.08,2.30,2.94,2.33;P<0.05)from 3 rd week in the model mice.The gait analysis test showed the increased step width of mice and the decreased step length in the model mice from 5 th week(t=2.46,2.35;P<0.05;t=2.17,3.35;P<0.05).The grab test showed the decreased grip from 3 rd week(t=2.19,2.51,2.81,3.32;P<0.05).The histopathology of substantia nigra of mice in the model group showed the progressive glial infiltration,nucleus sequestration,degeneration and death of neurons and reduced number of neurons from 3 rd week.Conclusion The PD-like characteristic changes gradually appear in PQ-induced PD mice from the third week.Glial activation may precede the degeneration and death of neurons in substantia nigra of mice.

关 键 词：百草枯 帕金森病 神经行为学 中脑黑质 

分 类 号：R114[医药卫生—卫生毒理学]