阿尔采末病

摘要： Alzheimer disease (AD) is a progressive neurodegenerative disease,and the pathogenic mechanism involves the accumulation and deposition of the amyloid-beta peptide (Aβ) in brain tissues.Aβ,the product of the large type1 trans-membrane protein amyloid precursor protein (APP),is generated in a two-step proteolytic process by β-secretase and followed by γ-secretase.As a β-secretase,β-site amyloid precursor protein-cleaving enzyme 1 (BACE1) is the rate-limiting enzyme of this process.Due to limiting its activity can prevent Aβ generation in AD,BACE1 has become an attractive therapeutic target for the treatment of AD.This review summarized the recent research and development of intervention strategies of BACE 1 in AD.%阿尔采末病(AD)是一种进行性的神经退行性疾病,其发病原因是脑内β淀粉样蛋白(Aβ)的聚集和沉积.Aβ是由淀粉样蛋白前体经β-分泌酶和γ-分泌酶剪切代谢生成,而β-淀粉样蛋白前体蛋白裂解酶1 (BACE1)是该过程的限速酶,抑制BACE1的活性可减少Aβ的产生,因此BACE1成为人们关注治疗AD的热门靶点.本文对近年来BACE1靶点在阿尔采末病治疗中的研究和进展进行综述.

摘要： 目的：探讨类叶升麻苷（acteoside，AS）对阿尔采末病（Alzheimer’s disease，AD）小鼠皮层组织中 Caspase-3基因表达的影响。方法将昆明（kunming，KM）小鼠随机分为正常组，模型组，vitamin E（VitE）组，类叶升麻苷低、中、高剂量组。除正常组外，其余各组小鼠均腹腔注射60 mg·kg －1· d －1的 D-半乳糖和灌胃5 mg·kg －1·d －1的三氯化铝，连续造模60 d 以制备 AD 模型。然后给以30、60、120 mg·kg －1·d －1的 AS 治疗30 d，期间造模继续。给药完成后，利用跳台法测定小鼠的学习和记忆能力，化学比色法测定小鼠血清及脑组织中的 AChE 活性；HE 染色观察各组小鼠皮层组织结构变化；免疫组化分析小鼠皮层组织中 caspase-3基因表达的变化。结果与模型组相比，AS 给药组小鼠的学习记忆能力有所改善，其下台潜伏期和错误次数均明显延长和减少（P ＜0.05或 P ＜0.01），血清和脑组织中 AChE 活性明显降低（P ＜0.05或 P ＜0.01），皮层组织中神经细胞的形态和数量明显改善（P ＜0.01），且皮层组织中 caspase-3基因表达明显下调（P ＜0.05或 P ＜0.01）。结论AS 对 D-半乳糖联合三氯化铝诱导的小鼠脑损伤具有明显保护作用，其保护机制可能是通过抑制小鼠皮层组织 caspase-3基因表达，进而维持皮层组织神经细胞的正常形态及数量。%Aim To investigate the effect of acteoside (AS)on the expression of caspase-3 in cerebral cortex of mouse models of Alzheimer’s disease(AD).Meth-ods Kunming (KM)strain mice were assigned into control group,model group,positive control group (VitE)and acteoside group.Every group was induced by a combination of D-galactose(i.p.60mg·kg -1 · d -1 )and AlCl3 (i.g.5mg·kg -1 ·d -1 )for 60ds ex-cept for control group,then mice were treated by dif-ferent concentrations(30,60,1 20 mg·kg -1 ·d -1 )of acteoside for 30ds.During the time,mice were in-duced continuously by a combination of D-galactose and AlCl3 .The learning and memory of mice were de-tected by step-down test,the activity of AChE in serum and brain of mice was measured by chemical colorime-try,the structure changes in cerebral cortex were ob-served by HE staining,and the expression of caspase-3 in cerebral cortex was analyzed through the immunohis-tochemical staining.Results Compared with model group,acteoside could improve the learning and mem-ory abilities(P <0.05 or P <0.01 ),decrease the ac-tivity of AChE in serum and brain(P <0.05 or P <0.01 ),and improve the morphology and number of neuron in cerebral cortex(P <0.01 ).Moreover,acte-oside could significantly inhibit the expression of caspase-3 in cerebral cortex (P <0.05,P <0.01 ). Conclusion Acteoside has significantly protective effects on brain damage of mice induced by a combina-tion of D-galactose and AlCl3 , and it′s protective mechanism probably relate to inhibiting the expression of caspase-3 and maintainings the normal morphology and number of neuron in cerebral cortex.

摘要： 目的 探讨雷公藤氯内酯醇(T4)对海马背侧注射Aβ25-35后模型大鼠神经元损伤的保护作用及可能机制.方法 通过Nissl和TUNEL染色法检测阳性神经元数量,采用免疫组化、蛋白印迹法观察ox-42、GFAP和p-p38MAPK的表达;ELISA法检测TNF-α、IL-1β的含量.结果 T4干预后(7 d),ox-42、GFAP、p-p38MAPK的表达减弱,Nissl阳性神经元增多,TUNEL阳性神经元减少,TNF-α、IL-1β的含量降低.结论 T4保护注射Aβ25-35后大鼠海马神经元损伤的机制可能与抑制小胶质细胞、星形胶质细胞和p38MAPK的激活有关.

摘要： 随着人口老龄化的不断发展,阿尔采末病(Alzheimer's disease,AD)已逐渐成为危害老年人健康的重大疾病之一,严重影响了患者的生活质量乃至生命安全,给家庭和社会带来沉重的生活及经济负担.因此,开发高效低毒的AD治疗药物目前已成为医学界面临的重大问题之一.中医药因其具有悠久的应用历史,在防治AD方面已逐渐获得全世界医学工作者的广泛关注.黄芩,作为传统中药之一,具有多种功效,应用范围较广.目前,越来越多的研究表明,黄芩及其提取物在改善学习记忆和治疗AD方面具有良好作用.该文从改善学习记忆、抗Aβ(Amyloid beta protein)沉积、抗神经细胞凋亡、促进神经细胞分化、保护线粒体、抗氧化、抗炎症等方面对黄芩及其提取物近5年来改善学习记忆和治疗AD的机制研究进展进行详细综述,以期为黄芩及其提取物在临床中改善学习记忆能力和治疗AD提供理论依据.

摘要： 阿尔采末病近年来发病率逐渐升高,对其发病机制的研究逐步深入.APP、PS1为已被明确的痴呆基因,γ-分泌酶是生成Aβ的限速酶,三者都是目前AD领域研究的热点,但是三者在AD间的具体相互作用机制及过程迄今还尚未明确,这些都可能是发现AD治疗新途径的潜在位点.

摘要： Methylglyoxal ( MG) , a toxic by-products of glycoly-sis, is widely distributed in human body. Under physiological conditions, only a little glucose is converted into MG. However, in disease or metabolic abnormalities, abnormal glycolysis causes MG to accumulate higher than the normal level. As high reactiveα-carbonyl aldehydes, MG can react with the long-lived protein to form Advanced Glycosylation End products(AGEs). MG and AGEs at the same time stimulate the cells to produce Reactive Oxygen Species ( ROS) and finally induce cell apoptosis. MG and its glycation activity are closely related with the genesis and development of various diseases including diabetes, vascular dis-ease, and neurodegenerative diseases. This article reviews the sources, metabolism and toxicity of MG, and summarizes the re-search advancement in several related diseases.%甲基乙二醛( methylglyoxal,MG)作为糖酵解过程固有的毒性副产物在人体内广泛分布。生理条件下,只有很少的葡萄糖会转变成MG。但在疾病或代谢异常的条件下,体内糖酵解发生异常,导致MG积累超过正常水平。 MG作为高反应活性的α-羰基醛,能够与长寿蛋白反应生成晚期糖基化终末产物( advanced glycosylation end products,AGEs)。同时MG和AGEs 均能刺激细胞产生活性氧( reactive oxygen species,ROS),最终诱发细胞凋亡。 MG及其糖化作用与糖尿病、血管病变和神经退行性病变等多种疾病的发生发展密切相关。该文对MG的来源、代谢和毒性进行阐述,并对其近年来在相关疾病中的研究进展进行总结。

摘要： Aim To explore the effects and mecha-nisms of choro-oxime derivatives on spatial learning and memory impairment in Kunming mice and SD rats induced by scopolamine and Aβ1-42 , respectively. Methods 40 Kunming mice were randomly divided into 5 groups: control group, model group, donepezil treatment group, arimoclomol treatment group and TCO-2 treatment group. There were 8 mice in each group. Mice of control group were established by intra-peritoneal injection of saline, and mice of other groups were injected with scopolamine and caused memory im-pairment. Both control group and model group were treated with solvent by intraperitoneal administration;donepezil treatment group received donepezil by intra-gastric administration; arimoclomol treatment group and TCO-2 treatment group were given the correspond-ing drugs by abdominal injection, respectively. The solvent and drugs were given at the same time every morning for 8 days. Spatial learning and memory abili-ty were tested by Morris water maze from the fifth day of the drugs administration. 40 SD rats were divided into 5 groups the same as the dementia model men-tioned above. Mice of control group were established by intracerebroventricular injection of saline, and mice of other groups were injected with insoluble Aβ1-42 to be induced of memory impairment. Solvent and drugs were also delivered as mentioned above. Morris water maze was carried out from the fifth day of the drug de-livery. After that, acetyl cholinesterase activity of hip-pocampus was tested with acetyl cholinesterase reagent kit; the content of Aβ1-42 in hippocampus was meas-ured by ELISA assay kit;the expression of phosphoryl-ated tau proteins was detected by Western Blot. Re-sults In both two dementia models, choro-oxime de-rivatives could improve the spatial learning and memory ability, shorten the escape latency and increase the times of crossing the former platform. Choro-oxime de-rivatives could also inhibit the acetyl cholinesterase ac-tivity in animal brain, decrease the concentration of Aβ1-42 and the expression of phosphorylated tau pro-teins in the dementia rats’ hippocampus. Conclusions Spatial learning and memory deficits induced by sco-polamine and Aβ1-42 could be reversed by choro-oxime derivatives. It may be concerned with enhancement of the cholinergic system functions and reduction of the levels of Aβ1-42 and phosphorylated tau proteins in the brain.%目的：研究氯肟衍生物arimoclomol和TCO-2对记忆障碍动物学习记忆能力的影响并初步探讨其机制。方法采用东莨菪碱致记忆获得性障碍小鼠模型和侧脑室注射 Aβ1-42所致记忆障碍大鼠模型。动物分为正常组、模型组、多奈哌齐对照组、arimoclomol 干预组和TCO-2干预组。正常组与模型组动物每日相同时间腹腔注射相应剂量的药物溶剂(生理盐水)；多奈哌齐对照组及待测药物干预组分别给予相应剂量的药物。给药8 d 后，采用Morris 水迷宫方法检测动物的空间学习记忆能力，并且检测动物海马组织的乙酰胆碱酯酶活性；检测侧脑室注射Aβ1-42大鼠海马组织的 Aβ1-42含量，并测定磷酸化tau 蛋白表达。结果与模型对照组相比，给予两种氯肟衍生物的动物搜索平台潜伏期缩短，穿越平台次数增加，表明氯肟衍生物可以明显改善注射东莨菪碱或Aβ1-42引起的记忆障碍；给予氯肟化合物还能够明显降低脑内乙酰胆碱酯酶活性和Aβ1-42含量，下调磷酸化 tau 蛋白的表达。结论氯肟衍生物可改善东莨菪碱以及侧脑室注射Aβ1-42所致的记忆障碍，其作用机制可能与增强中枢胆碱能系统功能、降低脑内Aβ蛋白和磷酸化tau 蛋白含量有关。

摘要： Sleep disorders are common diseases with various dys-function during sleep-wake process, including difficulty falling or staying asleep, falling asleep at inappropriate times, excessive total sleep time, or abnormal behaviors associated with sleep. Sleep disorders can lead to the deposition of amyloid beta protein ( Aβ) by affecting the normal metabolism of amyloid beta protein in the brain. Patients with Alzheimer’s disease ( AD) often suffer from sleep disorders, and its pathology always results in more se-vere sleep disorders, which leads to a risk of cognitive impair-ment and hypofunction. Sleep disorders could interact closely with AD, forming a positive feedback loop, which causes serious damage to the body health. This review summarized the current research about sleep disorder in the onset of AD and the current status of medication.%睡眠障碍系指睡眠-觉醒过程中表现出来的各种功能障碍,包括各种原因导致的失眠、过度嗜睡、睡眠呼吸障碍以及睡眠行为异常。睡眠障碍影响脑内β淀粉样蛋白( amy-loid beta protein, Aβ)的正常代谢,加速Aβ沉积。阿尔采末病(Alzheimer's disease, AD)患者常伴有睡眠障碍,AD患者的睡眠障碍会随着AD病情的发展而加重,对认知损伤、功能衰退都有一定影响。睡眠障碍与AD相互作用,形成正反馈环,严重危害机体健康。该文结合近来研究结果,对目前睡眠障碍与AD的相关研究及AD睡眠障碍药物治疗现状进行综述。

摘要： 糖原合成酶激酶-3β( glycogen synthase kinase-3β,GSK-3β)是一种丝氨酸/苏氨酸激酶,最初发现是糖原合成过程中的关键酶。在神经系统中,GSK-3β通过转录激活、细胞增殖与细胞分化参与神经系统的多种病理生理过程。 GSK-3β活性异常引起其下游的信号蛋白及基因表达异常,导致与其底物相关的如双极紊乱、精神分裂症、阿尔采末病及疼痛等多种神经精神疾病的发生。近年来, GSK-3β已成为基础和临床研究的热点,也逐渐成为众多疾病的治疗靶点。该文就GSK-3β参与神经精神疾病的机制做简要论述。%Glycogen synthase kinase-3β( GSK-3β) is a serine-threonine kinase,which was originally identified as a key regula-tor of glycogen metabolism. In nervous system, GSK-3β partici-pates in many central and peripheral nervous system physiological processes through transcription,cell proliferation and differentia-tion. The abnormal activity of GSK-3βinduces downstream signa-ling molecules and gene expression abnormalities,which are in-volved in some neuropsychiatric disorders such as schizophrenia, bipolar disorder,Alzheimer's disease,and pain. In recent years, lots of basic and clinic researches focus on GSK-3β,which might gradually become critical theraptic target of many diseases. The article mainly reviews the mechanisms involved in abnormal acti-vation of GSK-3β related neuropsychiatric disorders.

摘要： 目的：研究松果菊苷( ECH)对Aβ25-35引起的阿尔采末病( AD)大鼠的学习与记忆能力的改善和氧自由基水平的影响。方法60只SD大鼠,体质量(300依10) g,随机分为假手术组、模型组、ECH 高、中、低剂量组(40、20、10 mg ·kg-1·d-1)、阳性药石杉碱甲组(Hup-A,0.02 mg·kg-1·d-1)。水迷宫实验评价其学习记忆能力的改变。检测大脑皮质和海马中丙二醛( MDA)、一氧化碳( NO)的含量和超氧化物歧化酶( SOD)、一氧化氮合酶( NOS)的活性。结果 Aβ25-35能够严重损害大鼠学习记忆能力；与模型组大鼠相比,ECH不同剂量治疗组均能够减少其对学习记忆能力的损害(P<0.01, P<0.05)。 ECH治疗组大鼠大脑皮质和海马组织中的MDA含量明显下降,SOD的活性明显升高,明显减少NO、NOS的释放(P<0.01, P<0.05)。结论 ECH可以改善AD大鼠学习记忆力,其作用机制可能与加快氧自由基的清除能力和降低大鼠脑内氧化应激水平有关。%Aim To investigate the effects of echina-coside ( ECH ) on the learning and memory capacities and brain level of oxygen free radicals of rats with de-mentia induced by amyloid β-peptide. Methods Six-ty Sprague Dawley rats, weighing (300±10) g, were randomly divided with 10 rats pergroup into 6 groups:sham operated group, model, ECH high dose (40 mg ·kg-1·d-1), ECH middle dose (20 mg· kg-1· d-1), ECH low dose (10 mg·kg-1·d-1) and Hup A (Huperzine A, 0. 02 mg·kg-1·d-1) group. Mor-ris maze tests were conducted for evaluating the learn-ing and memory ability. Content of malondialdehyde (MDA), nitric oxide (NO) and activities of superox-ide dismutase ( SOD) and NO synthase ( NOS) in the hippocampus and cortex were detected. ResultsAβ25-35 induced significant learning and memory im-pairment in the rats. Compared with the rats in model group, those treated with ECH at different doses all manifested alleviation of learning and memory impair-ment ( P<0 . 01 , P<0 . 05 ) . Cotents of MDA of ECH treatment group were obviously decreased, while SOD activities were obviously increased, and significantly reduced the release of NO and NOS in the hippocam-pus and cortex brain tissue ( P <0 . 01 , P <0.05 ) . Conclusion ECH can enhance the learning and mem-ory ability in rats with AD, which is presumably relat-ed to accelerating the cleaning of oxygen free radicals and reducing oxidative stress in brain of AD rats.

摘要： 随着人口寿命延长和老龄化,老年痴呆(Alzheimer's disease,AD)已成为一个严重危害人类健康的社会问题.AD是发生在老年期和老年前期的一种慢性进行性退化性脑变性疾病,以进行性记忆减退、认知障碍和人格改变为主要特征.其主要病理改变为老年斑(SP)和神经原纤维缠结(NFT),主要发生在前脑基底、海马和大脑皮层.关于AD的发病机理一直是神经科学领域关注的焦点,虽然研究人员从神经病理学、生物学、基因学和病毒学等多方面进行了广泛的研究,但病因至今仍未完全明确.本文对同型半胱氨酸在阿尔采末病发病中的非血管机制进行了探讨。

摘要： 本发明公开了一种用于治疗阿尔采末氏病的中药单体组方，由以下配比的有效成分组成：人参皂甙Rg1 1.0～50mol、人参皂甙Re 1.0～50mol、人参皂甙Rb1 1.0～50mol；远志皂苷元Pre-Se 1.0～50mol。可采用常规加工方法，制成上述中药单体为主的注射剂、口服液、胶囊、片剂、提取物再混合等剂型。经研究证明本发明的中药单体组方可用于治疗阿尔采末氏病。本发明具有单体组方成分少，易于分离提取的优点，具有良好的市场前景，并且对于推动中药现代化有一定现实意义。

摘要： 本发明涉及一种煤矿井下巷道支护技术，具体是大采高末采综掘机做撤架通道过陷落柱架设无腿棚施工方法。具体为：在陷落柱区域进行常规支护，然后通过增加工字钢和单体柱，架设无腿棚，棚间通过拉杆固定成一个整体，无腿棚一端由液压支架支撑，另一端由单体柱支撑，与顶板固定紧密，综掘机在下方掘进时可以安全的进行作业。工作面顶板的稳固是影响煤矿安全的关键因素，本发明充分利用了液压支架和单体柱的支撑力，通过架设无腿棚，不仅缩短了施工工期，减轻了工人的劳动强度，而且提高了安全系数。

摘要： 本发明涉及煤炭采掘方法，具体为大采高工作面的采掘方法，有效解决了矿井开采中，现有的大采高工作面末采方法存在诸多缺陷的问题。一种大采高工作面快速末采方法，包括如下步骤：（1）合理设计和施工主撤通道：主撤通道采用宽×高为3.0～4.0×3.5～4.0m的断面设计；（2）提高主撤通道及采场周围相临巷道支护强度：主撤通道及采场周围相临巷道除采用锚网联合支护外，按留巷标准采用锚索加钢筋网补强支护，在主撤通道与工作面贯通侧顶板处施工锚索补强支护；（3）对主撤通道和三角区煤帮注化学浆。基于上述大采高工作面快速末采方法的工艺过程，使得工作面的末采可以顺利进行，且为后序撤架工作创造了良好条件。

摘要： 本发明提供利用细胞血液标志物用于早期诊断阿尔茨海默氏病和用于测定阿尔茨海默氏患者中针对阿尔茨海默氏病的治疗的功效(即监测阿尔茨海默氏病进展)的方法；以及用于进行这些方法的试剂盒。

摘要： 本发明公开了一种用于治疗阿尔采末氏病的中药单体组方，由以下配比的有效成分组成：人参皂甙Rg1 1.0～50mol、人参皂甙Re 1.0～50mol、人参皂甙Rb1 1.0～50mol；远志皂苷元Pre－Se 1.0～50mol。可采用常规加工方法，制成上述中药单体为主的注射剂、口服液、胶囊、片剂、提取物再混合等剂型。经研究证明本发明的中药单体组方可用于治疗阿尔采末氏病。本发明具有单体组方成分少，易于分离提取的优点，具有良好的市场前景，并且对于推动中药现代化有一定现实意义。

摘要： 结合淀粉样多肽Aβ的重组载脂蛋白E2(apoE2)

摘要： 本发明涉及一种煤矿井下巷道支护技术，具体是大采高末采综掘机做撤架通道过陷落柱架设无腿棚施工方法。具体为：在陷落柱区域进行常规支护，然后通过增加工字钢和单体柱，架设无腿棚，棚间通过拉杆固定成一个整体，无腿棚一端由液压支架支撑，另一端由单体柱支撑，与顶板固定紧密，综掘机在下方掘进时可以安全的进行作业。工作面顶板的稳固是影响煤矿安全的关键因素，本发明充分利用了液压支架和单体柱的支撑力，通过架设无腿棚，不仅缩短了施工工期，减轻了工人的劳动强度，而且提高了安全系数。

摘要： 本发明涉及一种采煤工艺，具体为一种大采高末采挂网工艺。了解决在煤矿采煤工作中，大采高末期的柔性网卷挂网的问题，步骤包括：将柔性网卷和支架组平行设置，所有支架立柱上安装一个手动绞盘，手动绞盘上连接钢丝绳，顶梁上安装滑轮；单数位架吊网，双数位架兜网； 开始割煤，割完后需要向前拉架；松开绞盘，使钢丝绳下落，将柔性网卷放下并且展开， 向前拉架，柔性网上边被固定，在拉架的过程中，展开部分的柔性网即可铺到顶板和支架顶梁之间的位置，在挂网前移过程中，在柔性网下面，挂横向的钢丝绳，和纵向钢丝绳，形成纵横的钢丝绳为骨架，柔性网为支撑的撤架通道结构。减少了金属网工艺工人扛网，趴网，上板梁等工艺，极大减轻了工人的劳动强度。最重要的是我们创新地使用钢丝绳加强了柔性网的强度，这样也保证了撤架工作的安全。

摘要： 本发明涉及煤炭采掘方法，具体为大采高工作面的采掘方法，有效解决了矿井开采中，现有的大采高工作面末采方法存在诸多缺陷的问题。一种大采高工作面快速末采方法，包括如下步骤：（1）合理设计和施工主撤通道：主撤通道采用宽×高为3.0～4.0×3.5～4.0m的断面设计；（2）提高主撤通道及采场周围相临巷道支护强度：主撤通道及采场周围相临巷道除采用锚网联合支护外，按留巷标准采用锚索加钢筋网补强支护，在主撤通道与工作面贯通侧顶板处施工锚索补强支护；（3）对主撤通道和三角区煤帮注化学浆。基于上述大采高工作面快速末采方法的工艺过程，使得工作面的末采可以顺利进行，且为后序撤架工作创造了良好条件。

摘要： 本发明涉及一种有效抑制阿尔采末病的药物，是按下面各中药质量份比组合而成：制首乌12份、钩藤12份、全蝎15份、生地15份、五味子10份、天麻12份、当归10份、香附10份、瓜萎15份、干姜6份、丹参12份、红枣15份、桃仁10份、郁金10份、枸杞子10份、肉苁蓉15份、甘草5份。发明人以中医学的观点分析了阿尔采夫病属于年迈肾虚致脏腑功能失调、气血两虚、阻闭经络，另一面，情志忧郁，肝脾失衡，水谷不化，痰浊内生致脉行涩滞必痴呆健忘，行为呆滞，采用以温阳补肾、益气养阴、活血通络、祛风化痰的中药结合治疗，不但能有益地抑制，还能延缓人的衰老。