《肠源性内毒素血症论文：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.doc》由会员分享，可在线阅读，更多相关《肠源性内毒素血症论文：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.doc（5页珍藏版）》请在taowenge.com淘文阁网|工程机械CAD图纸|机械工程制图|CAD装配图下载|SolidWorks_CaTia_CAD_UG_PROE_设计图分享下载上搜索。
1、肠源性内毒素血症论文：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【中文摘要】AD的发病机制尚不明确，A通过激活小胶质细胞而发生的脑内慢性炎性反响是AD发生开展的中心事件，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。为说明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
2、究方法(1)筛选研究对象及分组：依据纳入与排除标准，2021年1月2021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，否那么该样本不予录用。(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-8
3、0冻存备用。(5)检测指标：显色基质鲎试剂法检测LPS水平；ELISA法检测TNF-；ELISA法检测A1-42水平；ELISA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、临床病症、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2=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，P0.001)，而ADAS-Cog分数明显高于
4、对照组(t=18.067，P0.001)；(3) AD组LPS、TNF-、A1-42及Tau蛋白水平均明显高于对照组t=5.317、5.014、10.694、17.393，P0.001。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A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患者比拟差异显著，提示内毒素可能引起炎症反响，在AD发病中发挥重要作用。【英文摘要】The pathogenesis of AD is not clear yet. The chronic inflammatory respons
5、e in brain causedby Aactivating microglia is the center event in the development of AD, along with the wholeprocess of AD pathogenesis. Early animal experiments confirmed the AD rats were accompaniedwith intestinal endotoxemia (IETM). While, whether AD patients are also accompanied IETM?How does it
6、work then? If we confirm this argument, it will provide new ideas and theoreticalbasis for AD prevention and treatment.To observe the AD patients whether accompanied IETM, and further explore thepathogenesis in the course of AD. This will provide new thinking and theoretical basis forelucidating the
7、 pathogenesis of AD.Methods(1) Screen subject: Based on the inclusion and exclusion criteria, 80 elderly subje cts arecome from hospitals, communities and nursing homes in shanxi province between January 2021and January 2021. The topics have been approved by the Medical Ethics Committee of ShanxiMed
8、ical University, all selected samples signed informed consent by family members orguardians, and willing to participate in this research work, otherwise the sample is not to hire.(2) Collect general information: including gender, age, race, marital status, education level,family history, medical his
9、tory, vital signs and imaging data.(3) Neuropsychological tests: including the Mini Mental State Examination (MMSE) andAlzheimers Disease Assessment Scale cognitive subscale (ADAS-cog).(4) Blood collecting: venous blood 5ml in the morning and subjects on an empty stomach,then centrifuge within 2 hou
10、rs3500r/min，15min，4C, and remove supernatant (plasma) understerile conditions, then -80C frozen spare.(5) Detect indicators:LPS level was detected by Chromogenic End-point TachypleusAmebocyte Lysate (CE TAL);TNF-level was detected by ELISA;A1-42level wasdetected by ELISA;Tau protein level was detect
11、ed by ELISA.(6) Analysis the molecular mechanism of Alzheimer disease from multi- level andsystematic: use biological view, methods and combine with neuropathological features, clinicalsymptoms, neuroimaging, neuropsychological tests and molecular biological data levels describethe pathogenesis of A
12、lzheimers disease in systematic. Results(1) Gender (2=0.202，P=0.653)、age (t=1.266，P=0.209) and educational level (t=0.444，P=0.658) were no statistically significant between two groups.(2) MMSE scores in the AD group was significantly lower than the control group(t=16.473，P0.001); ADAS-Cog scores in
13、the AD group was significantly higher than thecontrol group (t=18.067，P0.001).(3) LPS, TNF-alpha , A1-42and Tau protein levels in AD group were significantly higherthan the control group (t=5.317、5.014、10.694、17.393，P0.001).ConclusionIn this study, we observed AD patients were complained with cognit
14、ive dysfunction,specificity of markers in the AD-Aand Tauprotein phosphorylation levels were significantlyincreased, further confirmed the accuracy of clinical diagnosis. At the same time, confirmed ADpatients existed intestinal endotoxemia (IETM), and compared with age of non-AD patients thediffere
15、nce was significant. It prompted endotoxin may cause inflammation, and played animportant role in AD pathogenesis.【关键词】肠源性内毒素血症 阿尔茨海默病 -淀粉样蛋白 Tau蛋白 小胶质细胞【英文关键词】Intestinal endotoxemia Alzheimers disease -amyloid Tau protein microglia【目录】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缩略表5-7中文摘要7-9Abstract9-10前言11-12研究目标12-13资料和方法13-163.1 研究对象133.2 主要测量工具、仪器和试剂13-143.3 研究方法14-163.4 统计学方法16结果16-194.1 AD 组与对照组一般资料的比拟16-174.2 AD 组与对照组的神经心理学测验结果174.3 AD 组与对照组血浆内毒素及肿瘤坏死因子- 水平的变化17-184.4 AD 组与对照组血浆 -淀粉样蛋白水平的变化18-194.5 AD 组与对照组血浆 Tau 蛋白水平的变化19讨论19-22结论22-24参考文献24-27附件27-32综述32-40参考文献37-40盲评评议书40-42个人简介42-43致谢43