塔依尔?吐尔松 阿地兰?沙拉木 兰希 孙龙飞 努尔买买提?艾买提

摘要：目的 觀察异常黏液质成熟剂对APP/PS1转基因阿尔茨海默病（AD）小鼠学习记忆和脑组织RAGE、LRP1蛋白表达的影响，探讨其作用机制。方法 选取3月龄APP/PS1转基因AD模型小鼠并将其随机分为模型组、阳性药组和异常黏液质成熟剂高、中、低剂量组，每组18只，另取18只3月龄C57BL/6J小鼠作为正常组。各给药组给予相应药物灌胃，连续6个月。跳台实验观察小鼠学习和记忆能力；免疫组化和Western blot检测LRP1、RAGE蛋白表达。结果 与正常组比较，模型组学习成绩反应期时间和错误次数增加，记忆成绩潜伏期时间减少、错误次数增加（P<0.01）；与模型组比较，各给药组学习成绩反应期时间和错误次数减少，记忆成绩潜伏期时间增加、错误次数减少（P<0.05，P<0.01）；免疫组化和Western blot结果显示，与正常组比较，模型组小鼠脑组织LRP1表达降低、RAGE表达增加（P<0.05）；与模型组比较，异常黏液质成熟剂各剂量组小鼠脑组织LRP1表达增加、RAGE表达降低（P<0.05，P<0.01）。结论 异常黏液质成熟剂可改善APP/PS1转基因AD小鼠空间学习记忆能力，调整RAGE和LRP1的表达。

关键词：异常黏液质成熟剂；APP/PS1转基因小鼠；空间学习记忆；海马CA1区；RAGE；LRP1

DOI：10.3969/j.issn.1005-5304.2017.03.011

中图分类号：R285.5 文献标识码：A 文章编号：1005-5304（2017）03-0043-05

Effects of Abnormal Phlegmatic Munziq on Ability of Learning and Memory and Protein Expressions of Brain Tissue RAGE and LRP1 of APP/PS1 Transgenic Mice Model of AD Tayerjan Tursun1， Adilan Shalamu2， LAN Xi2， SUN Long-fei3， Nurmuhammat Amat1 （1. Traditional Uyghur Medicine College， Xinjiang Medical University， Urumqi 830011， China； 2. The First Affiliated Hospital， Xinjiang Medical University， Urumqi 830011， China； 3. Traditional Chinese Medicine College ， Xinjiang Medical University， Urumqi 830011， China）

Abstract： Objective To investigate the effects of Abnormal Phlegmatic Munziq on ability of learning and memory， and protein expressions of brain tissue RAGE and LRP1 of APP/PS1 transgenetic mice model of AD； To discuss its mechanism of action. Methods Three-month-old APP/PS1 transgenic mice were randomly divided into 5 groups： model control group， positive control group， Abnormal Phlegmatic Munziq high-， medium-， and low-dose groups， 18 mice in each group. Another 18 three-month-old C57BL/6J mice were chosen as normal control group. All administration groups received relevant medicine for successive 6 months. Then the changes in ability of learning and memory of mice were detected by Step-down test； protein expressions of LRP1 and RAGE were detected by immunohistochemistry and Western blot. Results Compared with the normal control group， the reaction time of learning grades and the mistake times increased， incubation of memory grades decreased and the mistake times increased in the model control group （P<0.01）； Compared with the model control group， the reaction time of learning grades and the mistake times decreased， incubation of memory grades increased and the mistake times decreased in all administration groups （P<0.05， P<0.01）. Immunohistochemistry and Western blot results showed that compared with normal control group， the LRP1 expression decreased and RAGE increased in the model control group （P<0.05）；

基金项目：教育部新世纪优秀人才计划（NCET-11-1073）

通讯作者：努尔买买提·艾买提，E-mail：Oglan1972@126.com

Compared with the model control group， the LRP1 expression decreased and RAGE increased in Abnormal Phlegmatic Munziq high-， medium-， and low-dose groups （P<0.05，P<0.01）. Conclusion Abnormal Phlegmatic Munziq can improve ability of spatial learning and memory in APP/PS1 mice and regulate the expressions of RAGE and LRP1.

Key words： Abnormal Phlegmatic Munziq； APP/PS1 transgenic mice； spatial learning and memory； hippocampal CA1； RAGE； LRP1

阿尔茨海默病（Alzheimer's disease，AD）是一种神经系统退行性疾病，以多种原因引起的记忆和认知功能障碍及神经功能受损为主要特征。AD属于维医学异常体液所致“失忆”“失眠”“愚蠢”等范畴。在早期的轻度认知功能障碍期，异常黏液质在临床表现中占主要地位[1]。本实验观察异常黏液质成熟剂对APP/PS1转基因AD模型小鼠学习记忆和脑组织RAGE、LRP1蛋白表达的影响，探讨其作用机制。

1 实验材料

1.1 动物

3月龄APP/PS1转基因AD模型雄性小鼠90只，SPF级，体质量（25±2）g；3月龄SPF级C57BL/6J雄性小鼠18只，体质量（25±2）g，北京华阜康生物科技股份有限公司，动物许可证号SCXK（京）2009-0004。小鼠饲养于新疆医科大学SPF级实验动物中心。

1.2 药物

异常黏液质成熟剂，新疆医科大学维吾尔医学院；……