本文選題：異丙酚 + 空間學習記憶�。� 參考：《南方醫(yī)科大學》2014年碩士論文

【摘要】：背景 麻醉藥物和鎮(zhèn)靜藥物對于神經(jīng)系統(tǒng)的損害作用一直以來都是麻醉領域的研究熱點,異丙酚(propofol)是一種新型的短效靜脈麻醉藥物,廣泛應用于臨床麻醉誘導、維持及ICU鎮(zhèn)靜,具有起效快,麻醉狀態(tài)可控性強,維持時間短,蘇醒迅速,無積蓄,副作用小等優(yōu)點。 已有學者發(fā)現(xiàn)異丙酚可阻斷人的工作記憶,并可造成健忘癥的發(fā)生,但是Lee等的研究卻發(fā)現(xiàn)單次輸注異丙酚并不會引起成年和老年大鼠的記憶損害。然而在臨床上異丙酚的用途不僅是單次輸注,在全憑靜脈麻醉時及ICU內(nèi)可作為連續(xù)或間斷使用達數(shù)次或數(shù)小時乃至數(shù)天之久,因此僅憑單次輸注來判斷異丙酚是否具有學習、記憶能力損害作用并無實際意義。目前的臨床證據(jù)尚不足以證明異丙酚與學習、記憶能力損害之間存在因果關(guān)系,而臨床用藥的多樣性必然使得觀察人的神經(jīng)損害與異丙酚的關(guān)系復雜化,因此在積累臨床數(shù)據(jù)的同時,有必要通過進一步的動物實驗來研究異丙酚和神經(jīng)損害之間的關(guān)系和相應的機制。 哺乳動物成年神經(jīng)再生的發(fā)現(xiàn)顛覆了長久以來認為成年大腦不能產(chǎn)生新生神經(jīng)元的觀點。成年神經(jīng)再生,起源于神經(jīng)前體細胞,可在成年大腦的兩個區(qū)域發(fā)生：側(cè)腦室的腦室下區(qū)和海馬齒狀回區(qū)的背側(cè)區(qū)。成年神經(jīng)再生是神經(jīng)干細胞的增殖、分化、成熟及向神經(jīng)回路整合,產(chǎn)生新生神經(jīng)元的過程。海馬是哺乳動物邊緣系統(tǒng)的一個重要的結(jié)構(gòu),海馬的結(jié)構(gòu)內(nèi)部可分為齒狀回、CA1區(qū)、CA3區(qū)三個主要組成部分。海馬齒狀回區(qū)是哺乳動物成年期新生神經(jīng)元生成的幾個腦區(qū)之一,是在記憶過程尤其是建立和應用空間學習記憶時發(fā)揮重要作用的神經(jīng)集成網(wǎng)絡的重要組分。迄今為止,已知的麻醉藥物的作用機制主要是調(diào)控中樞神經(jīng)系統(tǒng)關(guān)鍵部位的突觸傳遞和神經(jīng)細胞膜上的離子通道。異丙酚也主要作用于突觸,調(diào)節(jié)突觸前膜遞質(zhì)的釋放和突觸前后膜Y-氨基丁酸受體的功能,從而產(chǎn)生中樞抑制效應,發(fā)揮麻醉作用。但是異丙酚具體作用的分子機制還不清楚。大部分在突觸傳遞中發(fā)揮重要作用的神經(jīng)遞質(zhì)和離子通道都是蛋白質(zhì)。蛋白質(zhì)是生命活動的最主要和最直接的體現(xiàn)者和執(zhí)行者,也是多種致病因素和藥物作用的靶分子。蛋白質(zhì)修飾尤其是磷酸化和去磷酸化作用,在不同的細胞功能如細胞分化、細胞生長、細胞凋亡等發(fā)揮重要作用。研究表明,阿爾茨海默病的腦組織的tau蛋白異常磷酸化作用發(fā)生在神經(jīng)纖維纏結(jié)之前,而且,經(jīng)過異氟醚和地氟醚吸入的動物體內(nèi)tau蛋白磷酸化作用增強,這種作用可能導致麻醉后短期認知功能障礙。因此發(fā)現(xiàn)異丙酚輸注后不同腦區(qū)磷酸化蛋白的水平的而變化對探討異丙酚的可能的神經(jīng)毒性機制是非常重要的。 大腦是一種高度交互的實體,一些獨立的大腦區(qū)域協(xié)作發(fā)揮生物學功能。丘腦被認為是皮質(zhì)下區(qū)和大腦皮層的信息傳遞部位。而且,功能性腦成像也證實丘腦是麻醉藥作用的主要腦區(qū)。研究顯示海馬主要負責心理思維過程,比如最初的學習記憶能力也包括意識行為。Wei等曾報道異丙酚可能由于其對學習記憶能力的影響,從而促進大鼠海馬CA1區(qū)突觸的長時程抑制的發(fā)展。大腦皮層是喚醒系統(tǒng)的最后的靶向腦區(qū),同時背外側(cè)的前額皮質(zhì)是大腦皮層最重要的部分,參與許多生理過程,如情感認知,隨意運動,工作記憶,甚至維持哺乳動物的激活狀態(tài)。 本研究第一部分通過Morris水迷宮實驗和免疫熒光技術(shù)及激光共聚焦技術(shù)來觀察異丙酚重復鎮(zhèn)靜對大鼠空間學習記憶能力和海馬齒狀回新生神經(jīng)元的影響,進一步探討異丙酚可能存在的神經(jīng)毒性作用。第二部分通過從異丙酚麻醉的動物模型中分離提取丘腦、海馬、額葉的磷酸化蛋白,然后用二維電泳和質(zhì)譜分析法篩選及鑒定異丙酚作用于不同腦區(qū)后對磷酸化蛋白表達水平的影響,為后續(xù)研究其相應的機制奠定基礎。 材料與方法 1.SD成年雄性大鼠分別腹腔給予異丙酚或脂肪乳,每天2次,持續(xù)7天。首先,應用Morries水迷宮實驗觀察和檢測大鼠給藥后28天的空間學習和記憶能力。其次,給藥后,經(jīng)腹腔注射BrdU標記,分別計數(shù)給藥后1天、14天和28天大鼠海馬齒狀回顆粒下區(qū)BrdU陽性細胞數(shù)。最后,應用激光共聚焦顯微鏡掃描給藥后14天大鼠新生神經(jīng)元的樹突長度和分枝數(shù)目。 2.SD成年雄性大鼠分別尾靜脈給予異丙酚或脂肪乳,20min后斷頭取丘腦、海馬、額葉。首先提取三個腦區(qū)磷酸化蛋白后雙向凝膠電泳檢測差異表達的磷酸化蛋白,然后用MALDI-TOF MS鑒定并在數(shù)據(jù)庫中搜索。最后Western Blot驗證差異表達的磷酸化蛋白。 結(jié)果 1.異丙酚鎮(zhèn)靜28天后,大鼠的逃逸潛伏期、游泳距離明顯延長,第5天在目標區(qū)域的停留時間明顯減少。異丙酚在給藥后第1天BrdU陽性細胞數(shù)無顯著差異,但是第14天和第28天則顯著減少。在給藥后第14天大鼠海馬齒狀回顆粒下區(qū)異丙酚組的DCX陽性細胞數(shù)顯著少于溶媒對照組,異丙酚組的DCX陽性新生神經(jīng)元的樹突長度和分枝數(shù)目顯著低于溶媒對照組。 2.雙向凝膠電泳顯示丘腦、海馬、額葉這三個腦區(qū)共有21個蛋白位點顯著不同,其中經(jīng)MALDI-TOF MS成功鑒定的有16個磷酸化蛋白位點。 討論 海馬是中樞神經(jīng)系統(tǒng)中參與認知功能如學習記憶能力等功能的最主要部位,海馬齒狀回區(qū)是生命活動中不斷產(chǎn)生新生神經(jīng)元的一個重要腦區(qū)。Deng等人綜述了許多關(guān)于新生神經(jīng)元對學習和記憶能力影響的報道,然而這些報道有些認為減少神經(jīng)再生會損害海馬依賴的學習和記憶能力,另一派則認為神經(jīng)再生的減少并不發(fā)揮什么作用。以往也有報道認為空間學習能促進新生神經(jīng)元增殖,增加新生神經(jīng)元的存活率,亦可能減少新生神經(jīng)元的數(shù)量。 因此,本研究旨在進一步探討新生神經(jīng)元與空間學習記憶能力的關(guān)系,以及異丙酚作用對其的影響。這些新生神經(jīng)元經(jīng)過神經(jīng)前體細胞的不斷增殖,形成神經(jīng)連接和突觸,逐漸成為具有記憶能力的成熟的神經(jīng)元。它們主要位于海馬齒狀回區(qū),大約4周后具有空間學習的能力。我們的結(jié)果發(fā)現(xiàn)異丙酚作用的大鼠在給藥后4周開始出現(xiàn)行為學損害,這也恰好是新生顆粒細胞具備參與到現(xiàn)有神經(jīng)環(huán)路中的能力的時候。并且,我們在給藥后分別計數(shù)了2組大鼠顆粒下區(qū)的BrdU陽性細胞數(shù)。在給藥后1天,兩組BrdU陽性細胞數(shù)的差異無統(tǒng)計學意義,說明異丙酚對于海馬成年神經(jīng)干細胞的增殖并無影響。然而在給藥后28天,異丙酚重復鎮(zhèn)靜組的大鼠顆粒下區(qū)BrdU陽性細胞數(shù)則顯著低于溶媒對照組,提示異丙酚可能損傷的是增殖中的細胞。這些結(jié)果表明異丙酚重復鎮(zhèn)靜可損害成年神經(jīng)再生,尤其是與學習能力密切相關(guān)的神經(jīng)前體細胞的存活,進而影響由神經(jīng)前體細胞增殖分化而成的神經(jīng)元的數(shù)量。 微管相關(guān)蛋白(doublecortin,DCX)作為神經(jīng)元前體細胞的標志物可以用來研究神經(jīng)元前體細胞的增殖和遷移。我們選擇DCX——成年海馬齒狀回新生神經(jīng)元可靠的標志物,對其進行免疫染色。并通過激光共聚焦顯微鏡比較了兩組DCX陽性新生神經(jīng)元的數(shù)量和發(fā)育狀態(tài)。異丙酚鎮(zhèn)靜組的DCX陽性細胞數(shù)在給藥后14天顯著減少,與BrdU陽性細胞計數(shù)的結(jié)果一致,表明該組神經(jīng)前體細胞存活較少。同時,該組的新生神經(jīng)元在形態(tài)學上的成熟度顯著延遲。我們的結(jié)果表明異丙酚鎮(zhèn)靜組新生神經(jīng)元的樹突結(jié)構(gòu)的復雜度,無論是在長度、分枝數(shù)目上均顯著減少。在神經(jīng)元的發(fā)育過程中,樹突結(jié)構(gòu)的復雜度是其成熟度的一個重要標志,同時也能夠說明其未來的學習能力。因此,由異丙酚鎮(zhèn)靜所造成的成年神經(jīng)再生能力的下降,不僅表現(xiàn)在神經(jīng)元的數(shù)量上,而且也造成了神經(jīng)元樹突成熟度的下降,由此亦不難推斷出其導致的行為學損害。 我們觀察了異丙酚重復鎮(zhèn)靜可損害大鼠空間學習和海馬區(qū)成年神經(jīng)再生,但異丙酚的這一作用并非通過損害成年神經(jīng)干細胞增殖,而是通過影響其存活率以及新生神經(jīng)元的樹突結(jié)構(gòu)引起的。但是異丙酚應用后所表現(xiàn)出的這種神經(jīng)毒性的具體機制還有待于進一步研究。 在本研究中我們采用蛋白質(zhì)組學方法篩選異丙酚作用后對丘腦、海馬、額葉中磷酸化蛋白的差異表達,經(jīng)過生物信息學分析和Western Blot驗證去探討異丙酚可能的作用機制。實驗結(jié)果發(fā)現(xiàn)異丙酚作用后有16種磷酸化蛋白表達水平存在差異,對差異表達的磷酸化蛋白進行生物信息學分析后,共發(fā)現(xiàn)6種蛋白質(zhì)：細胞角蛋白18(KRT18)、凝溶膠蛋白(GSN)、微管蛋白(TbB2C)、巨噬細胞加帽蛋白(MCP)、肌動蛋白(Actin)及載脂蛋白E(ApoE)可能與異丙酚的神經(jīng)毒性作用相關(guān),這些蛋白質(zhì)直接或間接的參與構(gòu)成了細胞骨架及其穩(wěn)定性的維持。 Tau蛋白是中樞神經(jīng)系統(tǒng)神經(jīng)元內(nèi)富含的II型微管結(jié)合蛋白(MAPs),它的磷酸化狀態(tài)可被一群特定的磷酸酶和磷酸激酶調(diào)節(jié),這些酶對維持神經(jīng)元的功能和發(fā)育有重要作用。Tau蛋白的高度磷酸化被認為與阿爾茨海默病(AD)和術(shù)后認知功能障礙的發(fā)病機制相聯(lián)系。七氟醚、異氟醚和異丙酚均可導致tau蛋白高度磷酸化,這可能可以解釋術(shù)后認知功能障礙的發(fā)生。ApoE也可在AD患者特有的淀粉樣斑塊和神經(jīng)纖維纏結(jié)中檢測到,參與AD的發(fā)病過程。ApoE4轉(zhuǎn)基因小鼠腦內(nèi)過度磷酸化的Tau蛋白的單體和多體的沉積表明ApoE能夠影響tau磷酸化的水平。我們推測異丙酚麻醉引起的術(shù)后認知功能障礙可能是由于血清ApoE水平變化導致的。然而這些因素的相互關(guān)系和ApoE磷酸化是否參與這個過程是未來需要探索的。 生物信息學分析顯示GSN和KRT18對酒精有反應。酒精能夠削弱機體對外界刺激的反應,類似于異丙酚麻醉后出現(xiàn)的行為學改變。氨基酸神經(jīng)遞質(zhì)受體在酒精依賴中起重要作用。酒精是GABA受體激動劑和NMDA受體拮抗劑,在大腦發(fā)育期通過抑制ERK磷酸化從而導致神經(jīng)系統(tǒng)的退行性變。大腦發(fā)育期酒精對大腦干細胞凋亡的影響作用也類似于異丙酚。海馬是大腦對酒精損害最敏感的區(qū)域,也是異丙酚麻醉作用的靶區(qū)域,谷氨酸是海馬環(huán)路輸入和輸出的主要神經(jīng)遞質(zhì)�？傊�,異丙酚的靶向區(qū)域和對信號傳遞的影響都與酒精相似。研究還表明酒精可能引起肝腎KRT18的磷酸化。我們的研究發(fā)現(xiàn),相比對照組,異丙酚給藥組的大鼠海馬區(qū)KRT18也發(fā)生了磷酸化改變。但是,具體的作用機制還需要進一步研究。 總而言之,本研究采用蛋白質(zhì)組學方法發(fā)現(xiàn)了丘腦、海馬、額葉的16種差異表達的磷酸化蛋白。同時使用生物信息學分析差異表達的磷酸化蛋白的共同特征去探討異丙酚作用于神經(jīng)系統(tǒng)的可能機制為進一步闡明異丙酚的神經(jīng)毒性機制提供了很有意義的參考。 結(jié)論 1.Morris水迷宮實驗表明異丙酚重復鎮(zhèn)靜可損害大鼠空間學習記憶能力,還可造成海馬齒狀回區(qū)的新生神經(jīng)元的數(shù)量下降以及樹突發(fā)育的不成熟,進而損害學習記憶能力。 2.異丙酚麻醉作用后可引起丘腦、海馬、額葉的KRT18,GSN, TbB2C, MCP,肌動蛋白,ApoE等細胞骨架蛋白質(zhì)的差異表達,這種異丙酚引起的蛋白質(zhì)磷酸化為未來研究異丙酚的神經(jīng)毒性機制提供了支持。
[Abstract]:background
The effect of narcotic drugs and sedative drugs on the nervous system has always been a hot spot in the field of anesthesia. Propofol (propofol) is a new type of short effective intravenous anesthetic. It is widely used in clinical anesthesia induction, maintenance and ICU sedation with rapid onset, strong controllability of narcotic state, short maintenance time, rapid recovery and no accumulation. It has the advantages of small side effect and so on.
Some researchers have found that propofol can block working memory and cause amnesia, but Lee studies have found that a single infusion of propofol does not cause memory damage in adult and old rats. However, the use of propofol in clinical use is not only a single infusion, but also in the case of intravenous anesthesia and in ICU. There is no practical significance in judging whether propofol is learning, and memory impairment is not practical. Current clinical evidence is not yet sufficient to demonstrate the relationship between propofol and learning and memory impairment, and the diversity of clinical medication inevitably leads to the view. The relationship between nerve damage and propofol is complex, so it is necessary to study the relationship and mechanism between propofol and nerve damage by further animal experiments while accumulating clinical data.
The discovery of adult nerve regeneration in mammals overturns the long-standing view that the adult brain does not produce new neurons. The adult nerve regeneration, originated from the neural precursor cells, can occur in two regions of the adult brain: the dorsal ventricle of the ventricle and the dorsal region of the dentate gyrus of the hippocampus. Adult neural regeneration is a neural stem cell. The hippocampus is an important structure of the mammalian marginal system. The internal structure of the hippocampus can be divided into three main parts of the dentate gyrus, CA1 area and CA3 region. The dentate gyrus of the hippocampus is one of the several brain regions of the newborn neurons of mammalian adults. It is an important component of the neural network, which plays an important role in the memory process, especially in the establishment and application of spatial learning and memory. So far, the mechanism of the known narcotic drugs is mainly to regulate the synaptic transmission in key parts of the central nervous system and the ion channels on the membrane of the nerve cell. The release of the transmitters of the presynaptic membrane and the function of the Y- aminobutyric acid receptor in the postsynaptic membrane produce the central inhibitory effect and play an anesthetic effect. However, the molecular mechanism of the specific action of propofol is not clear. Most of the neurotransmitters and ion channels, which play an important role in synaptic transmission, are proteins. The most important and direct embodying and executor of movement are also the target molecules of a variety of pathogenic factors and drug effects. Protein modification, especially phosphorylation and dephosphorylation, plays an important role in different cellular functions such as cell differentiation, cell growth, cell apoptosis and so on. Studies have shown that the tau eggs of Alzheimer's disease are in the brain tissue. White abnormal phosphorylation occurs before neurofibrillary tangles, and the enhanced phosphorylation of tau protein in animals inhaled by isoflurane and desflurane may lead to short-term cognitive impairment after anesthesia. Therefore, the changes in the level of phosphorylated protein in different brain regions after propofol infusion are found to be discussed in the study of propofol. The possible neurotoxicity mechanism is very important.
The brain is a highly interactive entity, and some independent brain regions collaborate to perform biological functions. The thalamus is considered to be the information transfer site of the subcortical and cerebral cortex. Moreover, functional brain imaging also confirms that the thalamus is the main brain area for the effect of anesthetics. Learning and memory ability also includes the awareness behavior.Wei and other reports that propofol may be affected by its learning and memory ability, thus promoting the development of long term depression in the synapse in the hippocampus CA1 region. The cerebral cortex is the final target brain area of the awakening system, while the dorsal frontal cortex is the most important part of the cerebral cortex, and participates in the involvement of the cerebral cortex. Many physiological processes, such as emotional cognition, voluntary movement, working memory, and even maintain the activation state of mammals.
In the first part of this study, the Morris water maze test, immunofluorescence technique and laser confocal technique were used to observe the effect of propofol repeated sedation on the spatial learning and memory ability of rats and the hippocampal gyrus rebirth neurons, and further explore the possible neurotoxicity of propofol. The second part passed the action of propofol anesthesia. The phosphorylated protein of the thalamus, hippocampus and frontal lobe was isolated and extracted from the model. Then two-dimensional electrophoresis and mass spectrometry analysis were used to screen and identify the effect of propofol on the expression of phosphorylated protein after the action of propofol on different brain regions, which laid the foundation for the subsequent study of its corresponding mechanism.
Materials and methods
1.SD adult male rats were given intraperitoneal injection of propofol or fat milk 2 times a day for 7 days. First, the Morries water maze test was used to observe and detect the spatial learning and memory ability of the rats at 28 days after administration. Second, after the administration, the BrdU markers were injected into the abdominal cavity for 1 days, 14 days and 28 days after the administration of the rat sea dentate gyrus. The number of BrdU positive cells in the region was measured. Finally, the number of dendritic cells and the number of branches of the newborn neurons were examined by confocal laser scanning microscope on the 14 day after administration.
The adult male rats of 2.SD were given propofol or fat milk respectively. After 20min, the thalamus, hippocampus and frontal lobe were taken out of the head. First, three phosphorylated proteins in the brain regions were extracted by two-dimensional gel electrophoresis to detect the differential expression of phosphorylated protein. Then, MALDI-TOF MS was identified and searched in the database. Finally, Western Blot was used to verify the differential expression of phosphoric acid. Protein.
Result
1. after 28 days of propofol sedation, the escape latency, swimming distance of the rats were obviously prolonged, and the stay time in the target area decreased significantly on the fifth day in the target area. The number of BrdU positive cells in the first days after the administration of propofol was not significantly different, but the fourteenth and twenty-eighth days decreased significantly. At fourteenth days after the administration, the D of the propofol group in the dentate gyrus of the rats The number of CX positive cells was significantly less than that of the control group. The number of dendritic cells and branches of DCX positive neurons in the propofol group was significantly lower than that in the solvent control group.
2. bi-directional gel electrophoresis showed that there were 21 different protein loci in the three brain regions of the thalamus, hippocampus and frontal lobe, of which 16 phosphorylated protein sites were identified by MALDI-TOF MS.
discuss
Hippocampus is the most important part of cognitive function, such as learning and memory ability in the central nervous system. The hippocampal dentate gyrus is an important brain area,.Deng, which produces new neurons in life activities. Many reports about the effects of new neurons on learning and memory ability are reviewed. However, these reports suggest that some of these reports have been reported. The reduction of nerve regeneration can damage the learning and memory ability of the hippocampus, while the other believes that the reduction of nerve regeneration does not play a role.
Therefore, the purpose of this study is to further explore the relationship between new neurons and spatial learning and memory, and the effect of propofol on them. These new neurons, through the continuous proliferation of neural precursor cells, form neural connections and synapses, and gradually become mature neurons with memory ability. They are mainly located in the dentate dentate shape of the hippocampus. Back area, about 4 weeks later, has the ability to learn in space. Our results found that the propofol action rats began to appear behavioral damage at 4 weeks after the administration, which was also the time when new granulosa cells had the ability to participate in the existing neural circuits. And we counted the BrdU Yang of the subregion of the 2 groups of rats after the drug was given. The number of BrdU positive cells in the two groups was not statistically significant at 1 days after the administration, indicating that propofol had no effect on the proliferation of adult neural stem cells in the hippocampus. However, the number of BrdU positive cells in the subgranular subgranular area of the propofol repeated sedative group was significantly lower than that of the dissolvent control group at 28 days after the administration, suggesting that propofol might be damaged. These results suggest that the repeated sedation of propofol can damage the regeneration of the adult nerve, especially the survival of the neural precursor cells, which are closely related to the learning ability, and then affect the number of neurons formed by the proliferation and differentiation of the neural precursor cells.
Doublecortin (DCX), as a marker of neuronal precursor cells, can be used to study the proliferation and migration of neuronal precursor cells. We choose DCX, a reliable marker of adult hippocampal dentate gyrus, and immunize them. And two groups of DCX positive freshmen are compared by light confocal microscopy. The number and development state of the neurons. The number of DCX positive cells in the propofol sedative group decreased significantly at 14 days after the administration, consistent with the results of the BrdU positive cell count, indicating that the group of neural precursor cells survived less. The complexity of the dendritic structure of newborn neurons, both in length and number of branches, is significantly reduced. In the development of neurons, the complexity of the dendritic structure is an important sign of its maturity, and it can also indicate its future learning ability. Therefore, the adult nerve regeneration ability caused by isopropanol sedation The decline is not only manifested in the number of neurons, but also causes the decline of dendrite maturity, so it is not difficult to deduce the behavioral damage caused by it.
We observed that propofol repeated sedation could damage spatial learning and adult neural regeneration in the hippocampus, but this effect of propofol is not by damaging the proliferation of adult neural stem cells, but by affecting the survival rate and the structure of the dendrites of newborn neurons. However, the neurotoxicity of propofol is shown after the use of propofol. The specific mechanism of sex remains to be further studied.
In this study, we used proteomic methods to screen the differential expression of phosphorylated proteins in the thalamus, hippocampus and frontal lobe after propofol action. Through bioinformatics analysis and Western Blot verification, we explored the possible mechanism of propofol. The experimental results showed that the expression level of 16 kinds of phosphorylated proteins was poor after the use of propofol. After bioinformatics analysis of differentially expressed phosphorylated proteins, 6 proteins were found: cytokeratin 18 (KRT18), GSN, microtubule protein (TbB2C), macrophage plus CAP protein (MCP), actin (Actin) and apolipoprotein E (ApoE), which may be related to the neurotoxicity of propofol. These proteins are direct Or indirect participation constitutes the maintenance of cytoskeleton and its stability.
Tau protein is a type of II microtubule binding protein (MAPs) rich in neurons in the central nervous system. Its phosphorylation state can be regulated by a group of specific phosphatase and phosphokinase. These enzymes play an important role in maintaining the function and development of neurons. The high phosphorylation of.Tau protein is considered to be associated with Alzheimer's disease (AD) and postoperative cognitive function. The pathogenesis of the disorder is linked. Sevoflurane, isoflurane, and propofol can lead to high phosphorylation of tau protein, which may explain the occurrence of postoperative cognitive dysfunction,.ApoE can also be detected in the amyloid plaques and neurofibrillary tangles endemic to AD patients, and is involved in the excessive phosphorylation of the brain in the.ApoE4 transgenic mice with the pathogenesis of AD. The deposition of the monomers and multibodies of Tau protein indicates that ApoE can affect the level of tau phosphorylation. We speculate that the postoperative cognitive dysfunction caused by propofol anesthesia may be caused by changes in serum ApoE levels. However, the relationship between these factors and whether the ApoE phosphorylation is involved in this process is to be explored in the future.

【學位授予單位】：南方醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2014
【分類號】：R614

【參考文獻】

相關(guān)期刊論文 前1條

1 ;Effects of intrathecal NMDA and AMPA receptors agonists or antagonists on antinociception of propofol[J];Acta Pharmacologica Sinica;2004年01期

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本文編號：1779206