AD患者血中内毒素、乙酰胆碱代谢酶活性、BDNF水平变化及其意义的研究

发布时间：2019-02-14 22:42

【摘要】：研究背景 阿尔茨海默病(AD)是老年人群中最常见的一种痴呆症,其特征性的病理变化：①p淀粉样蛋白(Ap)；②神经原纤维缠结(NFT)；③脑萎缩。迄今为止,AD的病因尚未阐明。我们前期动物实验证实了拟AD大鼠伴有肠源性内毒索血症(intestinal endotoxemia, IETM),在AD患者中也发现AD患者中伴有肠源性内毒素血症。但是,在IETM所伴AD中,乙酰胆碱酯酶(AChE)、胆碱乙酰转移酶(ChAT)、脑源性神经生长因子(BDNF)在其中扮演什么角色将是我们研究的内容。 研究目的 观察AD患者是否伴有IETM,进一步探讨AChE、ChAT、BDNF在AD发病中的作用机制,证实在AD发病中发挥重要作用。为寻找新的防治AD的发病提供新思路。 研究方法 (1)研究对象和分组：于2011年8月～2012年10月间将符合标准的山西医科大学第一医院、山西医科大学第二医院、山西省人民医院、太原市中心医院等太原市综合医院神经内科门诊、病房；精神科门诊、病房及山西省精神卫生中心门诊与病房、太原市老年病康复医院等70名老年人作为研究对象,分为老年痴呆组(AD组)和对照组。并收集一般资料：包括遗传史、既往史、年龄、民族、性别、教育水平、头颅CT或MRI检查结果。 (2)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)。 (3)收集血液标本：清晨6点,空腹,在肘静脉处抽取血液5m1,标本2小时内离心(3500转/分,15分,4℃),在-80℃冰箱内保存。 (4)检测指标：①显色基质鲎试剂法检测LPS水平；②ELISA法检测AChE、 ChAT、BDNF。 研究结果 (1)AD组MMSE分数明显低于对照组(t=15.357,P0.001),且ADAS-Cog分数明显高于对照组(t=17.382,P0.001)； (2)AD组血浆中LPS水平均明显高于对照组(t=3.926, P＜0.001); AChE水平高于对照组、ChAT水平明显低于对照组(t=0.017,P0.05；t=0.019,P0.001)；AD组血清BDNF水平明显低于对照组(t=0.010,P0.05)。 (3)由AD组LPS、BDNF、ChAT和AChE含量经统计学分析发现LPS在0.20Eu/ml以下时,BDNF、ChAT和AChE含量急速下降,当LPS在0.20Eu/ml以上时,BDNF、ChAT和AChE含量基本相近。由对照组LPS、BDNF、ChAT和AChE含量统计学分析发现,各变量间未发现变量间有相关关系存在。 研究结论 1.在AD的患者中有肠源性内毒素血症的发生。 2.本实验通过对AChE、ChAT、BDNF等的研究并结合课题组此前对TNFα、 Aβ、Tau蛋白的观察,提出了"IETM可能是AD发生过程中一个新的危险因素?”
[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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