本文關(guān)鍵詞： 神經(jīng)免疫調(diào)節(jié)網(wǎng)絡(luò)傳入通路 傳入信號(hào) 白細(xì)胞介素-1　出處：《中國(guó)協(xié)和醫(yī)科大學(xué)》2008年碩士論文　論文類型：學(xué)位論文

【摘要】： 神經(jīng)免疫學(xué)是二十世紀(jì)末期生命科學(xué)領(lǐng)域發(fā)展最為迅速的學(xué)科之一,神經(jīng)免疫學(xué)科的基礎(chǔ)理論“神經(jīng)—內(nèi)分泌—免疫調(diào)節(jié)網(wǎng)絡(luò)”學(xué)說已經(jīng)得到學(xué)術(shù)界的認(rèn)同。在“神經(jīng)—內(nèi)分泌—免疫調(diào)節(jié)網(wǎng)絡(luò)”研究的基礎(chǔ)上,相關(guān)的實(shí)驗(yàn)證明了神經(jīng)系統(tǒng)與免疫系統(tǒng)間存在功能調(diào)節(jié)作用。在神經(jīng)免疫調(diào)節(jié)網(wǎng)絡(luò)信號(hào)傳導(dǎo)的解剖學(xué)構(gòu)筑的研究中,調(diào)節(jié)網(wǎng)絡(luò)的功能相關(guān)的傳入信號(hào)和信號(hào)傳入通路構(gòu)成是領(lǐng)域研究爭(zhēng)論的焦點(diǎn)之一。本論文在課題組前期不同免疫狀態(tài)大鼠神經(jīng)免疫調(diào)節(jié)功能相關(guān)腦區(qū)的定位研究工作的基礎(chǔ)上,應(yīng)用蛋白質(zhì)組學(xué)研究中的表面加強(qiáng)激光解析電離—飛行時(shí)間—質(zhì)譜技術(shù)(SELDI-TOF-MS)和基質(zhì)輔助激光解析電離—飛行時(shí)間—質(zhì)譜技術(shù)(MALDI-TOF-MS)及雙向電泳(2-DE)分離技術(shù)等方法對(duì)不同免疫狀態(tài)大鼠的外周血清和腦脊液組份進(jìn)行比對(duì)分析,探索參與神經(jīng)免疫調(diào)節(jié)的上傳信號(hào)及傳入通路構(gòu)成模式,為進(jìn)一步闡明神經(jīng)免疫調(diào)節(jié)網(wǎng)絡(luò)的解剖學(xué)構(gòu)筑提供實(shí)驗(yàn)依據(jù)。 SELDI分析結(jié)果顯示,免疫組動(dòng)物外周血中觀察到221個(gè)有顯著性差異的信號(hào)峰,其中173個(gè)為表達(dá)量高于對(duì)照組的正向表達(dá)峰。實(shí)驗(yàn)各組大鼠腦脊液的分析結(jié)果未見有統(tǒng)計(jì)學(xué)意義的特異性差異峰表達(dá);在實(shí)驗(yàn)組血清中檢測(cè)到的特異性差異峰也未在腦脊液中觀察到相對(duì)應(yīng)的同步變化。在76個(gè)最高峰值為免疫2天的免疫功能相關(guān)性差異表達(dá)的免疫大鼠血清的信號(hào)峰中,根據(jù)差異信號(hào)峰的分子量、pI值和來源細(xì)胞在已知的神經(jīng)介質(zhì)、神經(jīng)肽、激素和細(xì)胞因子等信號(hào)物質(zhì)中進(jìn)行分析篩選,推測(cè)可能成為神經(jīng)免疫調(diào)節(jié)相關(guān)的傳入信號(hào)物質(zhì)。經(jīng)2-DE分離和MELDI-TOF-MS進(jìn)一步分析和鑒定免疫大鼠血清中18KD特異組份,分析報(bào)告了18種來源的19個(gè)相關(guān)肽段序列,共247氨基酸,但相關(guān)結(jié)果不能滿足任何已知物質(zhì)的氨基酸序列的排序。 我們的實(shí)驗(yàn)結(jié)果證明: 1)本論文采用SELDI技術(shù)對(duì)不同免疫狀態(tài)組大鼠和正常對(duì)照組大鼠的血清進(jìn)行對(duì)比分析的結(jié)果顯示實(shí)驗(yàn)組表達(dá)了221個(gè)與免疫功能相關(guān)的差異信號(hào)峰;差異信號(hào)表達(dá)峰值的分布在免疫2天的有76個(gè),免疫4天有1個(gè),免疫6天有96個(gè);差異峰值統(tǒng)計(jì)學(xué)分析具有極顯著性差異,某些差異峰的特異性甚至表現(xiàn)為“全或無”的關(guān)系。這些實(shí)驗(yàn)結(jié)果支持了神經(jīng)免疫調(diào)節(jié)網(wǎng)絡(luò)傳入信號(hào)模式研究中兩個(gè)重要的代表性假說——“血行傳導(dǎo)通路”和“神經(jīng)傳導(dǎo)通路”假說在神經(jīng)免疫調(diào)節(jié)網(wǎng)絡(luò)傳入信號(hào)通路領(lǐng)域研究中達(dá)成的共識(shí),即免疫活性細(xì)胞釋放功能活動(dòng)相關(guān)信號(hào)物質(zhì)到體液(血液)中,進(jìn)而啟動(dòng)神經(jīng)免疫調(diào)節(jié)功能。 2)對(duì)不同實(shí)驗(yàn)組大鼠的腦脊液組份對(duì)比分析的結(jié)果顯示,腦脊液中并不存在與免疫功能變化相關(guān)的神經(jīng)免疫調(diào)節(jié)功能的傳入信號(hào)物質(zhì),血液中免疫功能相關(guān)的信號(hào)物質(zhì)的變化沒有在腦脊液中平行反映。神經(jīng)免疫調(diào)節(jié)功能相關(guān)信號(hào)傳入模式不是“血液—腦脊液—接觸腦脊液的神經(jīng)元系統(tǒng)—中樞腦區(qū)”的血行傳導(dǎo)方式。本論文神經(jīng)免疫調(diào)節(jié)網(wǎng)絡(luò)信號(hào)傳導(dǎo)模式研究結(jié)果不支持“血行傳導(dǎo)通路”假說。 3)根據(jù)最高峰值在免疫2天的免疫功能相關(guān)的差異信號(hào)峰的分子量、PI值和來源細(xì)胞,在已知的神經(jīng)介質(zhì)、神經(jīng)肽、激素和細(xì)胞因子等信號(hào)物質(zhì)中進(jìn)行比對(duì)篩選,推測(cè)細(xì)胞因子IL-8、IL-15和IL-18等三個(gè)組份可能成為免疫系統(tǒng)釋放的跨系統(tǒng)傳遞的神經(jīng)免疫調(diào)節(jié)功能相關(guān)的傳入信號(hào)物質(zhì)。 4)本論文應(yīng)用蛋白質(zhì)組學(xué)研究技術(shù)的標(biāo)準(zhǔn)方法2-DE-MALDI-TOF-MS技術(shù)分析免疫大鼠血清中IL-1分子在神經(jīng)免疫調(diào)節(jié)網(wǎng)絡(luò)傳入通路中的地位和作用,發(fā)現(xiàn)免疫活性細(xì)胞釋放到血液中的IL-1不可能成為免疫系統(tǒng)釋放的跨系統(tǒng)傳遞的信號(hào)物質(zhì),參與神經(jīng)免疫調(diào)節(jié)網(wǎng)絡(luò)功能,否定了“血行傳導(dǎo)通路”和“神經(jīng)傳導(dǎo)通路”假說在神經(jīng)免疫調(diào)節(jié)網(wǎng)絡(luò)傳入信號(hào)通路領(lǐng)域研究中關(guān)于IL-1的共識(shí)。 5)對(duì)免疫大鼠血清雙向電泳分離的分子量約18KD,PI約5.0位置差異點(diǎn)進(jìn)行質(zhì)譜鑒定的結(jié)果顯示,該差異點(diǎn)的氨基酸序列不符合數(shù)據(jù)庫(kù)收集的任何已知物質(zhì)的氨基酸序列,提示神經(jīng)免疫調(diào)節(jié)網(wǎng)絡(luò)傳入通路的上傳信號(hào)中,可能包括我們還不了解的新物質(zhì)。
[Abstract]:Neuroimmunology is one of the most rapidly developing disciplines in the life sciences at the end of the twentieth century . The basic theory of neuroimmunology has been recognized by the academic community . In the study of nerve - endocrine - immune regulation network , the related experiments prove that there is a functional regulation between the nervous system and the immune system . The results of SELDI analysis showed that 221 signal peaks with significant difference were observed in the peripheral blood of the vaccinated group , 173 of which were positive expression peaks in the serum of the experimental group . Our experimental results demonstrate that : 1 ) The results of the comparative analysis of serum from different immune status group rats and normal control rats by SELDI technology show that the experimental group expresses 221 difference signal peaks related to immune function . The distribution of differential signal expression peak is 76 in the two days of immunity , there are 96 in 4 days of immunization and 96 in 6 days of immunization . These experimental results support two important representative hypothesis _ " blood line conduction path " and " nerve conduction path " in the study of the afferent signal pathway of the neural immunomodulatory network . These experimental results support the consensus that the immune active cells release the related signal substance into body fluid ( blood ) and then initiate the neuroimmunoregulation function . 2 ) The results of comparative analysis of cerebrospinal fluid in different experimental groups showed that there were no afferent signal substances related to immune function changes in cerebrospinal fluid . The changes of immune function - related signal substances in the blood were not reflected in the cerebrospinal fluid . 3 ) according to the molecular weight , PI value and source cell of the difference signal peak related to the immune function of the two - day immune function according to the highest peak value , three components such as IL - 8 , IL - 15 and IL - 18 in known nerve media , neuropeptides , hormones , cytokines and the like are compared and screened , and three components such as cytokines IL - 8 , IL - 15 and IL - 18 are presumed to be an incoming signal substance related to the neuroimmunoregulation function of the cross - system transmission released by the immune system . 4 ) In this paper , the status and function of IL - 1 molecule in the serum of immune rats were analyzed by using the standard method 2 - DE - MALDI - TOF - MS . It was found that IL - 1 released into the blood could not be a signal substance to be released by the immune system . 5 ) The results show that the amino acid sequence of the difference point does not conform to the amino acid sequence of any known substance collected in the database , suggesting that the amino acid sequence of the difference point does not conform to the amino acid sequence of any known substance collected by the database , suggesting that the uploading signal of the afferent pathway of the neural immunomodulatory network may include new substances that we don ' t know yet .

【學(xué)位授予單位】：中國(guó)協(xié)和醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2008
【分類號(hào)】：R392

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1 孔祥茜;神經(jīng)免疫調(diào)節(jié)網(wǎng)絡(luò)中傳入信號(hào)和信號(hào)傳導(dǎo)模式的研究[D];中國(guó)協(xié)和醫(yī)科大學(xué);2008年

2 洪禮傳;神經(jīng)免疫調(diào)節(jié)與神經(jīng)損傷相關(guān)信號(hào)研究[D];北京協(xié)和醫(yī)學(xué)院;2010年

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本文編號(hào)：1473610