發(fā)布時間：2018-08-04 14:40

【摘要】：AD的發(fā)病機制尚不明確，Aβ通過激活小膠質(zhì)細胞而發(fā)生的腦內(nèi)慢性炎性反應(yīng)是AD發(fā)生發(fā)展的中心事件，伴隨AD發(fā)病的全過程。前期動物實驗證實了擬AD大鼠伴有腸源性內(nèi)毒素血癥（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？如果我們證實了這一論點，那么將為AD的防治提供新的思路與理論依據(jù)。 研究目的 觀察AD患者是否伴有IETM，進一步探討其在AD發(fā)病中的作用機制，證實ET在AD發(fā)病中發(fā)揮重要作用。為闡明AD的發(fā)病機制提供新思路，最終為AD的防治提供新的理論依據(jù)。 研究方法 (1)篩選研究對象及分組：依據(jù)納入與排除標準，2011年1月～2012年1月將符合標準的太原市各醫(yī)院、養(yǎng)老院、社區(qū)等80名中老年人作為研究對象，分為AD組和正常對照組。所有入選樣本均由本人、家屬或監(jiān)護人知情同意，并簽署知情同意書，愿意參加本研究工作，否則該樣本不予錄用。 (2)收集一般資料：包括性別、年齡、種族、婚姻狀況、文化程度、家族史、既往病史、生命體征和影像學(xué)資料。 (3)神經(jīng)心理學(xué)測驗：簡易智能狀態(tài)檢查量表（MMSE）；阿爾茨海默病評定量表認知分量表（ADAS-cog）。 (4)采集血液：晨起采集研究對象（空腹）肘靜脈血液5ml，2小時內(nèi)離心（3500轉(zhuǎn)/分，15分，4℃），無菌條件下取上清（血漿），于-80℃凍存?zhèn)溆谩?(5)檢測指標：①顯色基質(zhì)鱟試劑法檢測LPS水平；②ELISA法檢測TNF-α；③ELISA法檢測Aβ1-42水平；②ELISA法檢測Tau蛋白。 (6)多層面、系統(tǒng)的分析阿爾茨海默病發(fā)病的分子機制：運用生物學(xué)的觀點和方法，結(jié)合神經(jīng)病理特征、臨床癥狀、神經(jīng)影像學(xué)、神經(jīng)心理測驗和分子生物等各層面的數(shù)據(jù)，，系統(tǒng)闡述阿爾茨海默病的發(fā)病機制。 研究結(jié)果 (1) AD組和正常對照組的年齡（t=1.266，P=0.209）、性別（χ2=0.202，P=0.653）、受教育年限（t=0.444，P=0.658）均無統(tǒng)計學(xué)意義； (2) AD組MMSE分數(shù)明顯低于對照組（t=16.473，P＜0.001)，而ADAS-Cog分數(shù)明顯高于對照組(t=18.067，P＜0.001)； (3) AD組LPS、TNF-α、Aβ1-42及Tau蛋白水平均明顯高于對照組（t=5.317、5.014、10.694、17.393，P＜0.001）。 研究結(jié)論 本實驗觀察到AD患者伴有認知功能減退，AD的特異性標志物—Aβ與Tau蛋白過度磷酸化水平明顯增加，進一步證實臨床診斷的準確性；同時，證實了AD患者存在腸源性內(nèi)毒素血癥，與同齡非AD患者比較差異顯著，提示內(nèi)毒素可能引起炎癥反應(yīng)，在AD發(fā)病中發(fā)揮重要作用。
[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

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