硝酸镧亚急性暴露对C57-ras转基因小鼠神经行为学及海马细胞形态学的影响  

Effects of lanthanum nitrate subacute exposure on neurobehavioral and hippocampal cell morphology of C57-ras transgenic mice

作　　者：韩高超 敬海明[1,2] 齐丽娟[2] 张文静 李子南[2] 高珊[2] 刘晶晶[2] 冯颖[2] 宁钧宇[1,2] 李国君[1,2] HAN Gao-chao;JING Hai-ming;QI Li-juan;ZHANG Wen-jing;LI Zi-nan;GAO Shan;LIU Jing-jing;FENG Ying;NING Jun-yu;LI Guo-jun(School of Public Health,Capital Medical University,Beijing 100069,China;Beijing Center for Disease Prevention and Control/Beijing Center of Preventive Medicine Research,Beijing Key Laboratory of Diagnostic and Traceability Technologies for Food Poisoning,Beijing 100013,China)

机构地区：[1]首都医科大学公共卫生学院,北京100069 [2]北京市疾病预防控制中心/北京市预防医学研究中心,食物中毒诊断溯源技术北京市重点实验室,北京100013

出　　处：《毒理学杂志》2021年第2期87-92,共6页Journal of Toxicology

基　　金：国家重点研发计划(2018YFC1603102,2018YFC1602703,2018YFC1602705)。

摘　　要：目的研究硝酸镧亚急性暴露对C57-ras转基因小鼠神经行为和海马细胞形态学的影响,初步探索ras基因在镧对小鼠海马结构与功能毒性效应中的保护作用。方法40只C57-ras转基因小鼠随机分为4组(雌雄各半),分别灌胃0、12.5、25和50 mg/kg·bw剂量的硝酸镧六水合物(以镧计算,分别为:4.01、8.02和16.05 mg/kg·bw)28 d;20只同窝野生型小鼠随机分为2组(雌雄各半),分别灌胃0和25 mg/kg·bw剂量的硝酸镧六水合物(以镧计算为8.02 mg/kg·bw)28 d。末次染毒后立即进行爬杆实验、衣架实验、Y迷宫和新物体识别实验,然后采集全血、取脑并分离海马组织。应用电感耦合等离子体质谱仪测定血液和脑中的镧含量,苏木素-伊红(HE)染色法观察海马CA3区病理改变。结果硝酸镧能被吸收入血并蓄积于小鼠脑组织,海马内的蓄积量高于其他脑区。与同基因型对照小鼠相比,同窝野生型小鼠染镧25 mg/kg·bw组的爬杆时长增加,衣架评分、自发交替反应率和偏好指数均降低(P<0.05),其海马组织出现病理学改变,CA3区神经元排列层次明显减少且出现紊乱,细胞脱失较为明显,不规则细胞增多;细胞核体积变小,深染,呈核固缩;还可见细胞变性,部分细胞质中尼氏体消失。与同基因型对照组相比,C57-ras转基因小鼠12.5和25 mg/kg·bw染镧组神经行为学表现均未受影响,海马组织未见明显病理改变;50 mg/kg·bw镧组小鼠海马神经元出现与野生型小鼠染镧25 mg/kg·bw组相似的病理损伤。结论亚急性硝酸镧暴露可以引起小鼠海马CA3区神经元病理改变,并损害小鼠的运动协调和空间学习记忆能力;而ras基因的过表达,在镧所致小鼠海马结构与功能损伤中具有一定的保护作用,其分子机制有待进一步研究。Objective To study the effects of lanthanum nitrate subacute exposure on C57-ras transgenic mice,and to explore the protective role of ras gene on lanthanum nitrate-induced damage to mice hippocampus.Methods Forty C57-ras transgenic mice were randomly divided into four groups(half male and female),and administrated by oral gavage with Lanthanum(Ⅲ)nitrate hexahydrate at doses of 0,12.5,25 and 50 mg/kg·bw(calculated by lanthanum,respectively:4.01,8.02 and 16.05)for 28 days;20 litter wild-type mice were randomly divided into two groups(half male and female),and were given lanthanum nitrate at doses of 0 and 25 mg/kg·bw(calculated by lanthanum as 8.02 mg/kg·bw)via oral gavage for 28 days.Rod climbing experiment,hanger experiment,Y maze and new object recognition test were performed immediately after the last exposure.The whole blood was collected.Then the mice were sacrificed,brains were taken out,and hippocampal tissues were separated.Inductively coupled plasma mass spectrometer was used to determine the contents of lanthanum in the blood and brain tissues,and the pathological changes in hippocampal CA3 area were observed by HE staining.Results Lanthanum can be absorbed into the blood by oral exposure and accumulated in the brain tissues.The accumulation in the hippocampus was higher than other brain regions.Compared with control mice with the same genotype,the climbing time of the wild-type mice exposed to lanthanum at 25 mg/kg·bw was increased,and the hanger score,spontaneous alternation reaction rate and preference index were all decreased(P<0.05).There were pathological changes in the hippocampus,and the neurons in the CA3 area disarranged,cell loss turned obvious,and irregular cells increased;the nucleus became smaller,deep stained,and nuclear pyknosis;Parts of Nissl bodies of the cytoplasm disappear.Compared with control mice with the same genotype,the neurobehavior of C57-ras transgenic mice treated with 12.5 and 25 mg/kg·bw lanthanum-exposed groups were not affected,and no obvious pathological changes

关 键 词：镧 C57-ras转基因小鼠 神经毒性 海马 

分 类 号：R114[医药卫生—卫生毒理学] R99[医药卫生—公共卫生与预防医学]