肠源性内毒素血症在阿尔茨海默病发病中的作用机制研究

发布时间：2018-08-04 14:40

【摘要】：AD的发病机制尚不明确，Aβ通过激活小胶质细胞而发生的脑内慢性炎性反应是AD发生发展的中心事件，伴随AD发病的全过程。前期动物实验证实了拟AD大鼠伴有肠源性内毒素血症（Intestinal endotoxemia，IETM），那么，AD患者是否也伴有IETM呢？它又是如何起作用的呢？如果我们证实了这一论点，那么将为AD的防治提供新的思路与理论依据。 研究目的 观察AD患者是否伴有IETM，进一步探讨其在AD发病中的作用机制，证实ET在AD发病中发挥重要作用。为阐明AD的发病机制提供新思路，最终为AD的防治提供新的理论依据。 研究方法 (1)筛选研究对象及分组：依据纳入与排除标准，2011年1月～2012年1月将符合标准的太原市各医院、养老院、社区等80名中老年人作为研究对象，分为AD组和正常对照组。所有入选样本均由本人、家属或监护人知情同意，并签署知情同意书，愿意参加本研究工作，否则该样本不予录用。 (2)收集一般资料：包括性别、年龄、种族、婚姻状况、文化程度、家族史、既往病史、生命体征和影像学资料。 (3)神经心理学测验：简易智能状态检查量表（MMSE）；阿尔茨海默病评定量表认知分量表（ADAS-cog）。 (4)采集血液：晨起采集研究对象（空腹）肘静脉血液5ml，2小时内离心（3500转/分，15分，4℃），无菌条件下取上清（血浆），于-80℃冻存备用。 (5)检测指标：①显色基质鲎试剂法检测LPS水平；②ELISA法检测TNF-α；③ELISA法检测Aβ1-42水平；②ELISA法检测Tau蛋白。 (6)多层面、系统的分析阿尔茨海默病发病的分子机制：运用生物学的观点和方法，结合神经病理特征、临床症状、神经影像学、神经心理测验和分子生物等各层面的数据，，系统阐述阿尔茨海默病的发病机制。 研究结果 (1) AD组和正常对照组的年龄（t=1.266，P=0.209）、性别（χ2=0.202，P=0.653）、受教育年限（t=0.444，P=0.658）均无统计学意义； (2) AD组MMSE分数明显低于对照组（t=16.473，P＜0.001)，而ADAS-Cog分数明显高于对照组(t=18.067，P＜0.001)； (3) AD组LPS、TNF-α、Aβ1-42及Tau蛋白水平均明显高于对照组（t=5.317、5.014、10.694、17.393，P＜0.001）。 研究结论 本实验观察到AD患者伴有认知功能减退，AD的特异性标志物—Aβ与Tau蛋白过度磷酸化水平明显增加，进一步证实临床诊断的准确性；同时，证实了AD患者存在肠源性内毒素血症，与同龄非AD患者比较差异显著，提示内毒素可能引起炎症反应，在AD发病中发挥重要作用。
[Abstract]:The pathogenesis of AD is not clear. The chronic inflammatory reaction of A 尾 by activating microglia cells is the central event of AD, which is accompanied by the whole process of AD. Previous animal experiments confirmed that AD rats were accompanied by Intestinal endotoxemia (IETM), and were AD patients accompanied with IETM? How does it work? If we confirm this argument, it will provide new ideas and theoretical basis for AD prevention and treatment. Objective to investigate the role of et in the pathogenesis of AD by observing whether AD patients are accompanied by IETMM and to confirm that et plays an important role in the pathogenesis of AD. In order to clarify the pathogenesis of AD and provide a new theoretical basis for the prevention and treatment of AD. Methods (1) screening of subjects and groups: according to the inclusion and exclusion criteria, 80 middle-aged and elderly people, including hospitals, nursing homes and communities in Taiyuan from January 2011 to January 2012, were selected as the subjects of the study. They were divided into AD group and normal control group. All the selected samples are informed consent of the person, family member or guardian, and sign informed consent form. They are willing to participate in this study. Otherwise, the sample will not be employed. (2) collect general information: sex, age, race, marital status, Education, family history, medical history, vital signs and imaging data. (3) Neuropsychological test: (MMSE); Alzheimer's disease rating scale cognitive subscale (ADAS-cog). (4) for blood collection: study subjects (fasting) cubital vein blood centrifuged within 2 hours (3500 rpm / min, 15 鈩

本文编号：2164195