Dou C S, Zhi C N, Liu W L, Fu J L, Yao B Y
School of Public Health, Peking University, Beijing 100191, China.
Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi. 2018 Feb 20;36(2):84-90. doi: 10.3760/cma.j.issn.1001-9391.2018.02.002.
To investigate the effect of manganese chloride (MnCl(2)) 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. Adult male C57BL/6 mice were treated with MnCl(2) 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. Compared with the control group, the high dose of MnCl(2) reduced body weight obviously (<0.01) . The results of vertical pole test showed that MnCl(2) 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 MnCl(2) 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 MnCl(2), comparing with controls (<0.05) . Moreover, the escape latency time of high dose MnCl(2) prolonged prominently comparing with MPTP grou (<0.05) . The results of histopathology showed that acidophilic changes elevated in MnCl(2) and MPTP group, comparing with controls. Furthermore, in striatum the oxyphil cells number increased in MnCl(2) high-dose group comparing with MPTP group (<0.01) . On the contrary, there were more oxyphil cells in MPTP group comparing with MnCl(2) groups in substantia nigra (<0.01) . Both manganese and MPTP can induce the impairment of dopaminergic neural system, but the symptons and injured location of manganism are inconsistent with PD models induced by MPTP.
研究氯化锰(MnCl₂)或1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)对C57BL/6小鼠神经行为和组织病理学的影响,为锰中毒的诊断、治疗和预防提供依据。成年雄性C57BL/6小鼠分别以5、10、20mg Mn/kg和30mg MPTP/kg的剂量腹腔注射MnCl₂和MPTP。对照组注射等量生理盐水。所有动物每周给药5次,连续给药4周,第5周进行行为测试后处死。分别通过垂直杆试验、旷场运动试验和Morris游泳任务测试平衡能力、焦虑抑郁水平和认知功能。使用光学显微镜通过HE染色病理切片检查纹状体和黑质的神经元病理变化。与对照组相比,高剂量MnCl₂明显降低体重(<0.01)。垂直杆试验结果显示,MnCl₂和MPTP延长了爬杆时间和转身时间。旷场运动试验表明,暴露于MnCl₂或MPTP后,运动距离、站立时间和中央场时间减少。在Morris游泳任务中,与对照组相比,注射MPTP以及高剂量MnCl₂后,逃避潜伏期延长,目标象限活动时间显著减少(<0.05)。此外,高剂量MnCl₂的逃避潜伏期比MPTP组显著延长(<0.05)。组织病理学结果显示,与对照组相比,MnCl₂和MPTP组嗜酸性变升高。此外,与MPTP组相比,MnCl₂高剂量组纹状体中嗜酸性细胞数量增加(<0.01)。相反,在黑质中,MPTP组的嗜酸性细胞比MnCl₂组更多(<0.01)。锰和MPTP均可诱导多巴胺能神经系统损伤,但锰中毒的症状和损伤部位与MPTP诱导的帕金森病模型不一致。