东莨菪碱长期给药致小鼠学习记忆障碍模型及机制研究  

Model and mechanism of scopolamine induced learning and memory impairment in mice

作　　者：刘淑青 顾丰华[1,2] LIU Shu-qing;GU Feng-hua(State Key Laboratory of&New Drug Pharmaceutical Process,Shanghai Institute of Pharmaceutical Industry,China State Institute of Pharmaceutical Industry,Shanghai 200437,China;Shanghai Professional and Technical Service Center for Biological Material Druggability Evaluation,Shanghai 200437,China)

机构地区：[1]中国医药工业研究总院上海医药工业研究院创新药物与制药工艺国家重点实验室,上海200437 [2]上海市生物物质成药性评价专业技术服务中心,上海200437

出　　处：《医学食疗与健康》2021年第2期1-6,共6页Medical Diet and Health

摘　　要：目的:考察东莨菪碱长期给药后对小鼠学习记忆功能的影响,探究东莨菪碱长期给药致小鼠学习记忆障碍模型的剂量效应关系及对神经再生和氧化损伤的作用。方法:ICR雄性小鼠,随机分为空白对照组、14天造模组和14天持续造模组。造模组分别腹腔注射东莨菪碱1 mg/kg、2 mg/kg、4 mg/kg,空白对照组腹腔注射等体积0.9%氯化钠溶液。通过Morris水迷宫实验、跳台实验检测小鼠学习记忆能力,BrdU+DCX染色检测小鼠脑神经元增殖分化情况,考察脑内乙酰胆碱酯酶(AChE)、超氧化物歧化酶(SOD)活性及丙二醛(MDA)含量变化。结果:东莨菪碱长期给药后可延长小鼠找寻水迷宫平台潜伏期,减少穿越平台次数,降低目标象限停留时间;减少跳台潜伏期,增加错误次数;可影响小鼠BrdU+DCX阳性细胞数;改变AChE、SOD活性及MDA含量;有剂量-效应关系。结论:东莨菪碱长期给药后可造成一定程度小鼠学习记忆功能障碍,且长期给药可致神经细胞损伤,其作用机制可能与神经细胞再生障碍和氧化损伤有关。Objective:To investigate the effects of scopolamine on learning and memory function of mice after long-term administration and explore the dose-effect relationship of long-term administration of scopolamine,as well as the effects on nerve regeneration and oxidative damage.Methods:Male ICR mice were randomly divided into a blank control group,a 14-day model group and a 14-day continuous model group.The model group was scopolamine by intraperitoneal injection at the doses of 1,2 and 4 mg/kg,and the blank control group was given the same volume of saline.Learning and memory ability of mice were investigated by Morris water maze experiment and diving platform experiment,and the proliferation and differentiation of brain neurons were detected by BrdU+DCX staining,and cholinesterase(AChE),superoxide dismutase(SOD)activity and malondialdehyde(MDA)content of brain were investigated.Results:Continuous administration of scopolamine could prolong the incubation period of finding the water maze platform,reduce the number of crossing the platform,and reduce the residence time of the target quadrant.And reduce the diving platform incubation period,increase the number of errors.The number of BrdU+DCX positive cells in mice was affected.AChE,SOD activity and MDA content were changed.There is a dose-effect relationship.Conclusion:Scopolamine can cause learning and memory dysfunction and nerve cell damage in mice after long-term,the mechanism of which may be related to nerve cell regeneration disorder and oxidative damage.

关 键 词：东莨菪碱 MORRIS水迷宫实验 免疫荧光染色 

分 类 号：R-332[医药卫生]