塔依尔?吐尔松 买吾拉尼江?依孜布拉 买地尼也提?尼亚孜 等

摘要：目的 观察异常黏液质成熟剂颗粒对APP/PS1转基因小鼠空间学习记忆、海马CA1区组织病理形态学变化的影响，探讨其作用机制。方法 选取3月龄APP/PS1转基因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。Morris水迷宫实验观察小鼠学习和记忆能力；HE染色光镜下观察海马CA1区病理形态；透射电镜观察小鼠海马CA1区有髓神经髓鞘、微管、微丝。结果 水迷宫实验结果显示，模型组小鼠逃避潜伏期时间较正常组明显延长（P<0.01），空间搜索实验穿越原平台位置次数较正常组明显减少（P<0.01）；与模型组比较，异常黏液质成熟剂除低剂量组第1日外其余各剂量组小鼠逃避潜伏期明显缩短（P<0.05，P<0.01），异常黏液质成熟剂低、高剂量组小鼠经过有效区域次数明显增加（P<0.05，P<0.01），异常黏液质成熟剂各剂量组小鼠原平台所在象限停留时间明显增加（P<0.01）。HE染色显示，异常黏液质成熟剂各组小鼠脑组织海马CA1区，锥体细胞层完整性稍好，细胞排列整齐，形态正常，均匀分布；电镜观察，与模型组比较，异常黏液质成熟剂各组小鼠海马CA1区神经元核形不规则，核膜清楚，染色质清晰，核仁明显，细胞基质均匀，细胞器丰富，分布均匀，线粒体嵴明显，粗面内质网和游离核糖体多见。结论 异常黏液质成熟剂颗粒可改善APP/PS1转基因小鼠空间学习记忆能力，减轻神经元超微结构受损。

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

DOI：10.3969/j.issn.1005-5304.2016.04.011

中图分类号：R285.5 文献标识码：A 文章编号：1005-5304（2016）04-0041-04

Effects of Abnormal Phlegmatic Temperament Granules on Behavioristics and Hippocampus Pathomorphism of APP/PS1 Transgenic Mice TURSUN Tayerjan1， HIZBULLA Mawlanjan1， NIYAZI Maidiniyeti2， SHAWUTI Shadike3， AMAT Nurmuhammat1 （1. Uygur Medical School， Xinjiang Medical University， Urumqi 830011， China； 2. First Affiliated Hospital of Xinjiang Medical University， Urumqi 830011， China； 3. Affiliated Chinese Medicine Hospital of Xinjiang Medical University， Urumqi 830000， China）

Abstract： Objective To investigate the effects of Abnormal Phlegmatic Temperament Granules on spatial learning and memory， histopathology morphological change in hippocampus CA1 zone； 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 （donepezil 0.92 mg/kg） group， Abnormal Phlegmatic Temperament Granules high-， medium-， and low-dose groups （3， 2， 1.5 g/kg）， 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 learning and memory ability of mice were detected by Morris water maze test； pathomorphism in hippocampus CA1 zone was detected by HE staining method； changes of myelin sheath， microtubule， and

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

microfilament in myelinated nerve of hippocampus CA1 zone were detected by electron microscope. Results Morris water maze test results showed that escape incubation period of APP/PS1 transgenic mice was significantly longer than the normal control group （P<0.01）， and the original platform time was significantly shorter than normal control group （P<0.01）； compared with model control group， Abnormal Phlegmatic Temperament Granules treatment groups escape latency time was significantly reduced （P<0.05， P<0.01）. Space experiments and escape incubation period of Abnormal Phlegmatic Temperament Granules high-， medium-， low-dose groups were significantly shortened （P<0.05， P<0.01）， and spatial searching test showed that the times of mice in Abnormal Phlegmatic Temperament Granules high-， medium-， low-dose groups passing through effective area increased （P<0.01）. The integrity of HE staining pyramidal cell layer in the hippocampus CA1 zones of Abnormal Phlegmatic Temperament Granules high-， medium-， and low-dose groups was relatively good； cells arranged orderly； distribution was normal. Electron microscopic observation showed that compared with model control group， the hippocampus neurons nuclear had irregular shape； nuclear membrane was clear and complete； chromatin was clear； nucleolus was obvious； cell matrix was uniform； organelles were abundant； mitochondrial cristae was obvious； endoplasmic reticulum and free ribosomes were obvious. Conclusion Abnormal Phlegmatic Temperament Granules can improve spatial learning and memory in APP/PS1 mice， alleviate neuronal ultrastructure damage and ultimately improve cognitive function.

Key words： Abnormal Phlegmatic Temperament Granules； APP/PS1 double transgenic mice model； spatial learning and memory； hippocampus CA1 zone

阿尔茨海默病（Alzheimer disease，AD），是以记忆力丧失、认知功能障碍为主要临床特征的神经退行性障碍疾病。近年来，AD的患病率和死亡率呈上升趋势，加之晚期AD患者常伴有严重认知功能障碍和精神异常症状，由此带来的社会、家庭、经济及公共卫生问题将会越来越严重。AD属维医中异常体液导致的“失忆”“失眠”“愚蠢”“遗忘”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的地位[1]。临床上异常黏液质成熟剂对AD早期疗效较好。本实验观察该药对APP/PS1转基因小鼠空间学习记忆能力和海马CA1区组织病理形态学变化的影响，探讨其作用机制。……