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1、阿尔茨海默病论文：阿尔茨海默病 -淀粉样蛋白 侧脑室持续灌注 海风藤 行为学【中文摘要】阿尔茨海默病(Alzheimer disease, AD)是一种以进行性认知功能障碍为主要表现的神经系统退行性疾病,其病理学特征是老年斑、神经原纤维缠结及神经元缺失。老年斑的主要成分是淀粉样蛋白(-amyloid protein,A)。虽然AD确实切病因及具体机制还不明确,但广泛认可的A假说认为,A主要由淀粉样蛋白前体蛋白(Aprecursor protein, APP)水解而产生,在机体内因代谢障碍而沉积在海马、基底核等部位,从而启动了AD的发病过程,并在其发生、开展中起关键作用。许多研究认为A1-42寡
2、聚体是AD发病中的主要毒性形式,其比聚合态A-42具有更高的神经毒性。本病认知缺陷的程度与脑内寡聚体的水平相关,而不是与总的淀粉样蛋白含量相关1。因此该实验同时使用A1-42寡聚体和聚合态A1-42来诱导大鼠的认知功能障碍,并观察两者之间对大鼠行为学影响程度的不同。近些年来,已建立了多种较公认的AD动物模型,然而现在还没有一种动物模型能够模拟AD患者所有的认知、行为、生化和组织病理学异常。使用微渗泵向侧脑室内持续灌注A能够局部模拟AD的病理表现,并且较好地解决了使大量A弥散性分布到脑内而不是在注射点局部聚集的问题,因而本实验采用侧脑室持续灌注A1-42方法建立AD研究的动物模型。海风藤属胡椒科
3、胡椒属植物,具有神经保护和抗炎作用。很多文献报道侧脑室持续灌注A后可以导致大鼠行为学改变,但海风藤能否减轻这些改变尚不清楚,因此将研究海风藤是否能改善模型大鼠学习记忆功能作为本课题的立项出发点。通过侧脑室持续灌注A142建立痴呆大鼠模型,采用水迷宫实验观察模型大鼠行为学改变以及海风藤对其影响,为说明AD发生机制及寻找干预措施提供依据,具有重要的理论意义和潜在的实用价值。探讨采用侧脑室持续灌注A1-42方法致SD大鼠AD模型的建立；探讨A1-42寡聚体与聚合态A1-42对大鼠行为学不同程度的影响；探讨应用海风藤干预后大鼠行为学是否发生变化。方法：60只SD大鼠随机分为10组,采用微渗泵向左侧侧脑
4、室持续灌注法制作动物模型。10组分别为：空白对照组(A组,不给于任何手术操作和干预)、假手术组(B组,只接受脑室内置管等手术操作,不给于药物)、聚合态A组(C组,脑室内灌注聚合态A+乙腈和三氟乙酸造模)、聚合态A+海风藤提取物组(D组,脑室内灌注聚合态A+乙腈和三氟乙酸)、聚合态A+DMSO组(E组,脑室内灌注聚合态A+乙腈和三氟乙酸)、乙腈和三氟乙酸组(F组,脑室内灌注乙腈和三氟乙酸,而不注射A)、A寡聚体组(G组,脑室内灌注A寡聚体+HDL和HEPES造模)、A寡聚体+海风藤提取物组(H组,脑室内灌注A寡聚体+HDL和HEPES)、A寡聚体+DMSO组(组,脑室内灌注A寡聚体+HDL和(?
5、)IEPES)、HDL和HEPES组(J组,脑室内灌注HDL和(?)HEPES,而不注射A寡聚体)。术后D组和H组大鼠每天腹腔注射10%海风藤提取物(含2.5%DMSO),每100g体重1ml,E组和组大鼠每天腹腔注射2.5%DMSO,共5周。术后第31天起进行Morris(?)迷宫实验,分为空间探索期和定向航行期。空间探索实验时记录逃避潜伏期,定向航行实验时录制实时视频,并分析计算穿越平台的次数,在平台所在象限经历的时间比率和路程比率。结果：(1)水迷宫实验空间探索期G组逃避潜伏期比C组延长(PO.05),C组潜伏期比F组延长(P0.05),G组潜伏期比J组延长(P0.05)；D组比C组、E
6、组逃避潜伏期缩短(P0.05)；H组比G组、组逃避潜伏期缩短(P0.05)；A组、B组、F组和J组之间逃避潜伏期无明显差异。(2)水迷宫实验定向航行期G组穿越平台的次数少于C组,时间比率和路程比率低于C组(P0.05)；C组穿越平台的次数少于F组,时间比率和路径比率低于F组(P0.05)；G组穿越平台的次数少于J组,时间比率和路程比率低于J组(P0.05)；D组穿越平台的次数多于C组、E组,时间比率和路程比率高于C组、E组(P0.05)；H组穿越平台的次数多于G组、组,时间比率和路程比率高于G；组、组(P0.05)；A组、B组、F组和J组之间无明显差异。结论：向一侧侧脑室持续灌注A1-42能建
7、立AD动物模型；A1-42寡聚体对大鼠行为学的影响较聚合态A1-42对大鼠行为学的影响大；海风藤干预能局部改善A1-42组大鼠的学习记忆能力。意义：本研究使用大脑立体定位技术通过微渗泵向SD大鼠左侧侧脑室持续灌注A1-42寡聚体或者聚合态A1-42,建立老年性痴呆动物模型,术后给予海风藤提取物进行干预,采用Morris水迷宫实验观察海风藤提取物对模型大鼠行为学的影响,为揭示AD发病机制和寻找有效的AD干预措施提供依据,具有重要的理论意义和潜在的应用价值。【英文摘要】Background:Alzheimers disease(AD) is a kind of neurodegenerative
8、disease with progressive cognitive impairment as the main manifestation. Pathological characteristic of AD is the formation of senile plaques, neurofibrillary tangles and neuronal and synaptic loss in specific brain regions.-amyloid (A) is the main component of senile plaques. Althouth the definite
9、etiological factor and the concrete pathogenesis of AD is not confirmed,hypothesis related to Aargues that A,mainly produced by the hydrolysis of Aprecursor protein(APP),deposites in such structures as hippocampus and basal nucleus due to dysmetabolisism,thus initiate the pathological process of AD.
10、 Several researches found that A1-42 oligomer is the main toxic form of AD,and has a more neurotoxic effect than fibrillar A1-42 dose.The extent of cognitive impairment is related to the level of A1-42 oligomer rather than the level of the total Aamount.This study used A1-42 oligomer and fibrillar A
11、1-42 to induce the cognitive impairment and analized the impact of the two forms of A1-42 on the cognition respectively.Recently,many AD animal model have been used but none could completely simulate every aspect of AD including abnormality of biochemistry、pathology、behavior and cognition. Continuou
12、s intracerebroventricular infusion of AP could partly duplicate the pathological manifestation of AD,and a mount of Adistributes diffusely in the brain rather than resembles in the local injectional site.so animal administrated with continuous intracerebroventricular infusion of Acan act as animal m
13、odel for AD research.Piper kadsura ohwi is thought to have anti-inflammation and neuroprotection function.Numerous researches published told us that continuous intracerebroventricular infusion of Acan induce the change of the ethology of AD model rat,but whether or not piper kadsura ohwi can improve
14、 these change isnt clear to us. So this sdudy is aimed at the effect of piper kadsura ohwi on the change of the ethology of A-induced AD model rat. Therefore, it is important theoretical significance and potential applications to find the effective intervention measure. :To explore the establishment
15、 of AD animal model in the way of continuous intracerebroventricular infusion of A; To explore the impact of A1-42 oligomer and fibrillar A1-42 on the ethology of model rat;To explore whether or not piper kadsura ohwi can ameliorate the ethological changes.Methods:60 SD rats were randomly divided in
16、to 10 groups (n=6) and received continuous intracerebroventricular infusion of Athrough mini-osmotic pump:normal control group(A group,received no surgery and treatment)、sham operation group(B group,received the implantation of infusion kit and mini-osmotic pump,no reagent)、fibrillar Agroup(C group,
17、received continouse infusion of fibrillar AP and methyl cyanides and TFA)、fibrillar Aand kadsura pepper group(D group, received fibrillar Aand methyl cyanides and TFA、fibrillar Aand DMSO(E group, received fibrillar Aand methyl cyanides and TFA)、methyl cyanides and TFA group(F group,received methyl c
18、yanides and TFA、Aoligomer group(G group, received Aoligomer and HDL and HEPES)、Aoligomer and kadsura pepper group(G group,received Aoligomer and HDL and HEPES)、Aoligomer and group(H group,received Aoligomer and HDL and HEPES)、Aoligmer and DMSO group(I group,received Aoligomer and HDL and HEPES)、HDL
19、and HEPES group(J group、received HDL and HEPES).After sugery, rats of D group and H group received intraperitoneal injection of 10% piper kadsura ohwi extract(containing 2.5% DMSO) everyday, 1ml per 100g weight,and as control groups, rats from E group and I group received intraperitoneal injection o
20、f 2.5% DMSO, 1ml per 100g weight.The treatment last 5 weeks. Morris water maze experiment began on the 31nd day after surgery,and comprised two phasesacquisition trials and probe trial.During acquisition trials, escape latency was recorded. During probe trial,real-time video was recorded,and the pro
21、portion of time and path spent in the target quadrant in which the hidden escape platform was previously located was noted,the times the rat swam through where the hidden escape platform was also noted.Results:(1) acquisition trials:escape latency was longer in G group than that in C group(P0.05),an
22、d escape latency was longer in C group than that in F group(P0.05), escape latency was longer in G group than that in J group (P0.05);compared with C group and E group, the escape latency in D group was shorter(P0.05); compared with G group and I group, the escape latency in H group was shorter (P0.
23、05); there was no significant difference between A group, B group, F group and J group.(2) probe trial:the times rat swam through where the hidden escape platform was in G group was less than that in C group, the proportion of time and path spent in the target quadrant in G group were lower than tha
24、t in C group (P0.05); the times rat swam through where the hidden escape platform was in C group and G group was less than that in F group and J group respectively (P0.05), the proportion of time and path spent in the target quadrant in C group and G group were lower than that in F group and J group
25、 respecively(P0.05);the times rat swam through where the hidden escape platform was in D group was more than that in C group and E group, the proportion of time and path spent in the target quadrant in D group were higer than that in C group and E group (P0.05);the times rat swam through where the h
26、idden escape platform was in H group was more than that in G group and I group, the proportion of time and path spent in the target quadrant in H group were higer than that in G group and I group (P0.05); there was no significant difference between A group, B group, F group and J group.Conclusions:C
27、ontinuous intracerebroventricular infusion of A(3 can establish AD animal model; A1-42 oligomer had a more severe impact on the ethology of AD model rats than fibrillar A1-42 did; piper kadsura ohwi may ameliorate the ethological changes of AD model rats.【关键词】阿尔茨海默病 -淀粉样蛋白 侧脑室持续灌注 海风藤 行为学【采买全文】 1.3.
28、9.9.38.8.4.8 1.3.8.1.13.7.2.1同时提供论文写作定制和论文发表效劳.保过包发.【说明】本文仅为中国学术文献总库合作提供，无涉版权。作者如有异议请与总库或学校联系。【英文关键词】Alzheimers disease piper kadsura ohwi beta- amyloid Continuous intracerebroventricular infusion the ethological changes【目录】海风藤提取物对AD模型大鼠行为学影响的研究摘要6-9ABSTRACT9-11符号说明12-13前言13-15材料与方法15-20实验结果20-21讨论21-25结论25-26附图26-27附表27-29参考文献29-33综述33-51参考文献43-51致谢51-52攻读硕士研究生期间参与实施的课题52-53学位论文评阅及辩论情况表53