锰中毒和PD模型小鼠神经行为改变及损伤部位的比较研究  

作　　者：窦长松 智翠娜 刘文丽[1] 付娟玲 姚碧云[1] 

机构地区：[1]北京大学公共卫生学院毒理系、食品安全毒理学研究与评价北京市重点实验室,100191

出　　处：《中华劳动卫生职业病杂志》2018年第2期84-90,共7页Chinese Journal of Industrial Hygiene and Occupational Diseases

基　　金：国家自然科学基金（No.81172693）;北京市自然科学基金（No.7152084）

摘　　要：目的探讨锰中毒和PD模型小鼠神经行为学及组织病理学的异同，为锰中毒的诊断和防治提供依据。方法成年C57BL/6雄性小鼠共80只，随机分为5组，每组16只，MnCl2低、中、高剂量组分别腹腔注射5、10、20 mg/kg MnCl2，PD模型组腹腔注射30 mg/kg MPTP，对照组注射等量生理盐水，5次/周，连续4周，每天观察动物一般情况。注射结束1周后，通过爬杆实验、旷场实验、水迷宫实验检测小鼠平衡协调能力、焦虑抑郁状态以及学习记忆等神经行为学改变；处死动物，显微镜下观察纹状体及黑质H-E染色病理切片，检查神经细胞病理变化。结果与对照组比较，MnCl2高剂量组小鼠体重明显降低，差异有统计学意义（P〈0.01）。与对照组比较，MnCl2和MPTP组小鼠爬杆实验总时间和转身时间明显增加差异均有统计学意义（P〈0.05），MnCl2中、高剂量组和MPTP组小鼠旷场实验穿过格子数、站立次数以及中央场活动时间明显减少（P〈0.05），MnCl2高剂量组及MPTP组小鼠水迷宫实验逃避潜伏时间增加且目标象限活动时间减少，差异均有统计学意义（P〈0.05）。与MPTP组比较，MnCl2高剂量组逃避潜伏时间明显增加，差异有统计学意义（P〈0.05）；病理结果显示，与对照组比较，MnCl2及MPTP组嗜酸性水平增高，其中纹状体嗜酸性细胞数MnCl2高剂量组高于MPTP组，差异有统计学意义（P〈0.01），黑质嗜酸性细胞MnCl2组少于MPTP组，差异有统计学意义（P〈0.01）。结论锰和MPTP均可引起多巴胺能神经系统损伤，锰中毒导致的神经行为学改变及损伤部位与MPTP诱导的PD模型不完全一致。ObjectiveTo investigate the effect of manganese chloride（MnCl2）or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine（MPTP）on the neurobehavioral and histopathology in C57BL/6 mice and provide evidence for the diagnosis,treatment and prevention of manganism. MethodsAdult male C57BL/6 mice were treated with MnCl2 and MPTP respectively by intraperitoneal injection at the doses of 5,10,20mg Mn/kg and 30mg MPTP/kg.Controls were injected equivalent normal saline.All animals were administrated 5 times a week for 4 consecutive weeks and sacrificed after behavior tests on the fifth week.Balance ability,anxiety and depression level and cognitive function were tested respectively by vertical pole test,open field locomotion test and Morris swim task.The neuron pathological changes of striatum and substantia nigra were examined through HE-staining pathological section by using optical microscope. ResultsCompared with the control group,the high dose of MnCl2 reduced body weight obviously（P〈0.01）.The results of vertical pole test showed that MnCl2 and MPTP lengthened the pole-climbing time and turnaround time.Open field locomotion test showed that movement distance,stand-up time and central field time were decreased after the exposure of MnCl2 or MPTP.In the Morris swim task,the escape latency time increased and the target quadrant activity time decreased significantly after the injection of MPTP as well as high-dose MnCl2,comparing with controls（P〈0.05）.Moreover,the escape latency time of high dose MnCl2 prolonged prominently comparing with MPTP grou（P〈0.05）.The results of histopathology showed that acidophilic changes elevated in MnCl2 and MPTP group,comparing with controls.Furthermore,in striatum the oxyphil cells number increased in MnCl2 high-dose group comparing with MPTP group（P〈0.01）.On the contrary,there were more oxyphil cells in MPTP group comparing with MnCl2 groups in substantia nigra（P〈0.01）.ConclusionBoth manganese and MPTP can induce the impairment of dopaminergic neural system,

关 键 词：锰 1-甲基-4-苯基-1 2 3 6-四氢吡啶 神经行为学 纹状体 黑质 C57BL/6小鼠 

分 类 号：R135.1[医药卫生—劳动卫生] R-332[医药卫生—公共卫生与预防医学] R742.5