【摘要】：研究背景 阿爾茨海默病(AD)是老年人群中最常見(jiàn)的一種癡呆癥,其特征性的病理變化：①p淀粉樣蛋白(Ap)；②神經(jīng)原纖維纏結(jié)(NFT)；③腦萎縮。迄今為止,AD的病因尚未闡明。我們前期動(dòng)物實(shí)驗(yàn)證實(shí)了擬AD大鼠伴有腸源性?xún)?nèi)毒索血癥(intestinal endotoxemia, IETM),在AD患者中也發(fā)現(xiàn)AD患者中伴有腸源性?xún)?nèi)毒素血癥。但是,在IETM所伴AD中,乙酰膽堿酯酶(AChE)、膽堿乙酰轉(zhuǎn)移酶(ChAT)、腦源性神經(jīng)生長(zhǎng)因子(BDNF)在其中扮演什么角色將是我們研究的內(nèi)容。 研究目的 觀察AD患者是否伴有IETM,進(jìn)一步探討AChE、ChAT、BDNF在AD發(fā)病中的作用機(jī)制,證實(shí)在AD發(fā)病中發(fā)揮重要作用。為尋找新的防治AD的發(fā)病提供新思路。 研究方法 (1)研究對(duì)象和分組：于2011年8月～2012年10月間將符合標(biāo)準(zhǔn)的山西醫(yī)科大學(xué)第一醫(yī)院、山西醫(yī)科大學(xué)第二醫(yī)院、山西省人民醫(yī)院、太原市中心醫(yī)院等太原市綜合醫(yī)院神經(jīng)內(nèi)科門(mén)診、病房；精神科門(mén)診、病房及山西省精神衛(wèi)生中心門(mén)診與病房、太原市老年病康復(fù)醫(yī)院等70名老年人作為研究對(duì)象,分為老年癡呆組(AD組)和對(duì)照組。并收集一般資料：包括遺傳史、既往史、年齡、民族、性別、教育水平、頭顱CT或MRI檢查結(jié)果。 (2)神經(jīng)心理學(xué)測(cè)驗(yàn)：簡(jiǎn)易智能狀態(tài)檢查量表(MMSE);阿爾茨海默病評(píng)定量表認(rèn)知分量表(ADAS-cog)。 (3)收集血液標(biāo)本：清晨6點(diǎn),空腹,在肘靜脈處抽取血液5m1,標(biāo)本2小時(shí)內(nèi)離心(3500轉(zhuǎn)/分,15分,4℃),在-80℃冰箱內(nèi)保存。 (4)檢測(cè)指標(biāo)：①顯色基質(zhì)鱟試劑法檢測(cè)LPS水平；②ELISA法檢測(cè)AChE、 ChAT、BDNF。 研究結(jié)果 (1)AD組MMSE分?jǐn)?shù)明顯低于對(duì)照組(t=15.357,P0.001),且ADAS-Cog分?jǐn)?shù)明顯高于對(duì)照組(t=17.382,P0.001)； (2)AD組血漿中LPS水平均明顯高于對(duì)照組(t=3.926, P＜0.001); AChE水平高于對(duì)照組、ChAT水平明顯低于對(duì)照組(t=0.017,P0.05；t=0.019,P0.001)；AD組血清BDNF水平明顯低于對(duì)照組(t=0.010,P0.05)。 (3)由AD組LPS、BDNF、ChAT和AChE含量經(jīng)統(tǒng)計(jì)學(xué)分析發(fā)現(xiàn)LPS在0.20Eu/ml以下時(shí),BDNF、ChAT和AChE含量急速下降,當(dāng)LPS在0.20Eu/ml以上時(shí),BDNF、ChAT和AChE含量基本相近。由對(duì)照組LPS、BDNF、ChAT和AChE含量統(tǒng)計(jì)學(xué)分析發(fā)現(xiàn),各變量間未發(fā)現(xiàn)變量間有相關(guān)關(guān)系存在。 研究結(jié)論 1.在AD的患者中有腸源性?xún)?nèi)毒素血癥的發(fā)生。 2.本實(shí)驗(yàn)通過(guò)對(duì)AChE、ChAT、BDNF等的研究并結(jié)合課題組此前對(duì)TNFα、 Aβ、Tau蛋白的觀察,提出了"IETM可能是AD發(fā)生過(guò)程中一個(gè)新的危險(xiǎn)因素?”
[Abstract]:Background Alzheimer's disease (AD) is the most common type of dementia in the elderly. Its characteristic pathological changes are as follows: 1 amyloid (Ap); 2 neurofibrillary tangle (NFT); 3 brain atrophy. To date, the etiology of AD has not been clarified. Our previous animal experiments confirmed that (intestinal endotoxemia, IETM), with enterogenous endotoxemia was also found in AD patients with AD in AD rats. However, the role of brain derived nerve growth factor (BDNF) in acetylcholinesterase (AChE), choline acetyltransferase (ChAT), brain-derived nerve growth factor (BDNF), will be the subject of our research. Objective to investigate the role of AChE,ChAT,BDNF in the pathogenesis of AD and to confirm that it plays an important role in the pathogenesis of AD. To find a new way to prevent and treat AD. Methods (1) study objects and groups: from August 2011 to October 2012, the first Hospital of Shanxi Medical University, the second Hospital of Shanxi Medical University, the people's Hospital of Shanxi Province, which met the criteria, were selected. Department of Neurology, Taiyuan City General Hospital; Seventy elderly patients were divided into senile dementia group (AD group) and control group (control group). General data were collected, including genetic history, past history, age, ethnicity, sex, educational level, cranial CT or MRI results. (2) Neuropsychological test: mini-mental state examination scale (MMSE);), cognitive subscale of Alzheimer's disease scale (ADAS-cog). (3) Blood samples were collected: blood was drawn from cubital vein at 6 o'clock in the morning on an empty stomach and centrifuged (3500 rpm, 15 min, 4 鈩，

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