摘要
目的在前期构建锰中毒动物模型并证实锰损害血脑脊液屏障和多巴胺神经元的研究基础上,本研究进一步评价亚急性染锰后大鼠锰内暴露情况及锰对大鼠血脑脊液屏障功能和神经行为的影响。方法 50只SD大鼠,雌雄各半,随机分为对照组(生理盐水)与染毒组[氯化锰,MnCl2,6 mg (Mn)/kg·bw,1次/d],腹腔注射染毒30 d。染毒期间每周记录大鼠体重和平衡木评分,末次染毒后立即进行Y迷宫和新物体识别实验,24 h后采集血清和脑脊液、分离黑质和纹状体。应用生化分析仪和ELISA法分别测定血清、脑脊液中的白蛋白含量,电感耦合等离子体质谱仪测定血清、脑脊液以及黑质与纹状体中的金属离子含量。结果大鼠经腹腔注射6 mg (Mn)/kg·bw 30 d后,血清和脑脊液的锰内暴露量为3.1~4.2(μg/L),比对照组高310%~740%。黑质、纹状体中锰的含量比对照组升高400%~640%,无明显性别差异。染锰大鼠血清中铜离子升高,雄性染锰大鼠纹状体铁离子升高,雌性纹状体锌、铜、镁和钙离子升高(P<0.05)。染锰组大鼠脑脊液中白蛋白指数升高,提示锰对血脑脊液屏障功能有不良影响。染锰组大鼠平衡木行走评分降低,Y迷宫中认知安全臂的错误数增加(P<0.05),但新物体学习记忆探索次数无明显变化(P>0.05)。雌性染锰大鼠Y迷宫主动回避次数降低(P<0.05)。结论本研究对大鼠进行6 mg(Mn)/kg·bw的亚急性腹腔注射染毒,发现大鼠血清、脑脊液中锰增高,血脑脊液屏障功能受损,黑质和纹状体锰蓄积,大鼠出现神经行为改变。
Objective To study the effects of 30-day manganese exposure on internal exposure, blood cerebrospinal fluid barrier function and neurobehavior in rats. Methods SD rats were injected intraperitoneally with MnCl2 6 mg(Mn)/kg·bw for 30 days. The body weight and Beam Balance Test were recorded weekly. Y-maze test and novel object recognition test were measured after the last Mn exposure, then serum, cerebrospinal fluid, substantia nigra and striatum were collected.Serum albumin and CSF albumin were determined by biochemical and ELISA. Determination of metal content in these tissues using ICP-MS. Results After intraperitoneal injection MnCl2 for 30 days, in MnCl2 group Mn concentration in serum and cerebrospinal fluid was 3.1~4.2(μg/L), 310%~740% higher than control group, in the striatum and substantia nigra it was 400%~640% higher than control group. In MnCl2 group Cu, Fe in serum was increased, Fe in striatum of male MnCl2 group increased, and zinc, copper, magnesium, and calcium ions in female MnCl2 group striatum higher than control group(P<0.05). The increase of the albumin index in the cerebrospinal fluid indicates that manganese has an adverse effect on the blood-cerebrospinal fluid barrier function. The Beam Balance Test score of rats in the exposure group decreased, and the number of errors in the Y-maze test increased(P<0.05), but the number of errors in novel object recognition test did not change significantly(P>0.05). The number of correct times in the Y-maze test were reduced in Female MnCl2 group rats(P<0.05). Conclusion MnCl2 6 mg(Mn)/kg·bw ip. exposure for 30 days led to increase the manganese in the serum and cerebrospinal fluid of rats, causing damage to the blood-cerebrospinal fluid barrier function, and alteration of rats’ behavior.
作者
何雨欣
冯颖
刘晶晶
宁钧宇
刘丽萍
李子南
高珊
韩高超
张文静
敬海明
李国君
HE Yu-xin;FENG Ying;LIU Jing-jing;NING Jun-yu;LIU Li-ping;LI Zi-nan;GAO Shan;HAN Gao-chao;ZHANG Wen-jing;JING Hai-ming;LI Guo-jun(School of Public Health,Capital Medical University,Beijing 100069,China;Beijing Key Laboratory of Diagnostic and Traceability Technologies for Food Poisoning,Beijing Center for Disease Prevention and Control/Beijing Center of Preventive Medicine Research,Beijing 100013,China)
出处
《毒理学杂志》
CAS
CSCD
2020年第3期197-202,227,共7页
Journal of Toxicology
基金
国家重点研发计划(2018YFC1602705,2018YFC1603102)
国家自然科学基金(81373028)
北京自然科学基金(7164266)
北京市财政项目(环境健康风险评估技术与应用研究)。
关键词
锰
神经毒性
血脑脊液屏障
Manganese(Mn)
Neurotoxicity
Blood-cerebrospinalfluid barrier(BCB)
