本文選題：反復(fù)輕度腦創(chuàng)傷 + 神經(jīng)行為學(xué)��； 參考：《天津醫(yī)科大學(xué)》2017年碩士論文

【摘要】：研究目的:腦創(chuàng)傷(traumatic brain injury,TBI)因其高致殘、高致死的特點(diǎn),嚴(yán)重危害著人類(lèi)的健康,已成為全世界第三大疾病。近年來(lái),一種與反復(fù)輕度腦創(chuàng)傷(repetitive mild traumatic brain injury,rmTBI)相關(guān)的神經(jīng)退行性疾病——慢性創(chuàng)傷性腦病(chronic traumatic encephalopathy,CTE)得到了研究學(xué)者們?cè)絹?lái)越多的關(guān)注,該疾病常見(jiàn)于退伍士兵、橄欖球運(yùn)動(dòng)員、拳擊選手等。現(xiàn)階段,相關(guān)研究主要集中于CTE相關(guān)的rmTBI模型中行為學(xué)和病理學(xué)的研究,而CTE相關(guān)的rmTBI模型的免疫學(xué)研究尚未報(bào)道,屬于目前科學(xué)研究的空白領(lǐng)域。本實(shí)驗(yàn)首先通過(guò)改進(jìn)的神經(jīng)功能評(píng)分(mNSS)和Morris水迷宮實(shí)驗(yàn)(MWM),證實(shí)rmTBI大鼠模型存在長(zhǎng)時(shí)程的神經(jīng)行為學(xué)異常和認(rèn)知功能障礙,其次運(yùn)用免疫熒光術(shù)和流式細(xì)胞術(shù)初步研究rmTBI大鼠模型中T細(xì)胞亞群(CD3~+T細(xì)胞、CD3~+CD4+T細(xì)胞、CD3~+CD8+T細(xì)胞)以及小膠質(zhì)細(xì)胞表型(M1型小膠質(zhì)細(xì)胞、M2型小膠質(zhì)細(xì)胞)的變化規(guī)律,以了解CTE相關(guān)rmTBI大鼠模型中長(zhǎng)時(shí)程免疫反應(yīng)的變化規(guī)律,為進(jìn)一步探索其免疫機(jī)制奠定實(shí)驗(yàn)基礎(chǔ),同時(shí)也為進(jìn)一步探討CTE相關(guān)的新穎免疫防治策略提供理論依據(jù)。研究方法:1.mNSS和MWM評(píng)價(jià)大鼠rmTBI傷后42d內(nèi)的神經(jīng)行為學(xué)功能和認(rèn)知學(xué)習(xí)水平。2.應(yīng)用流式細(xì)胞儀檢測(cè)大鼠rmTBI傷后腦組織以及外周血中1d、3d、7d、14d、28d以及42d的T細(xì)胞亞群(主要集中在CD3~+T細(xì)胞、CD3~+CD4+T細(xì)胞、CD3~+CD8+T細(xì)胞)的變化規(guī)律。3.應(yīng)用免疫熒光、流式細(xì)胞儀檢測(cè)大鼠rmTBI傷后腦組織中7d、14d、28d及42d的小膠質(zhì)細(xì)胞表型(M1型小膠質(zhì)細(xì)胞、M2型小膠質(zhì)細(xì)胞)的變化規(guī)律。結(jié)果:1.(1)mNSS表明,大鼠rmTBI傷后42d內(nèi)存在明顯的神經(jīng)行為學(xué)異常。(2)MWM表明,大鼠rmTBI傷后存在長(zhǎng)時(shí)程的認(rèn)知功能障礙。2.(1)大鼠rmTBI傷后,存在長(zhǎng)時(shí)程中樞免疫功能的異常,T細(xì)胞(CD3~+T細(xì)胞)百分率呈雙峰型趨勢(shì),在7d和42d顯著上升。T細(xì)胞中CD3~+CD4+T細(xì)胞的百分率在傷后7d上升,之后持續(xù)下降。T細(xì)胞中CD3~+CD8+T細(xì)胞的變化趨勢(shì)恰與CD3~+CD4+T細(xì)胞的變化趨勢(shì)相反。(2)外周免疫中,T細(xì)胞(CD3~+T細(xì)胞)的百分率在傷后7d、14d均有顯著的上升,在傷后28d、42d均有顯著的下降。T細(xì)胞中CD3~+CD4+T細(xì)胞的百分率在傷后持續(xù)下降。T細(xì)胞中CD3~+CD8+T細(xì)胞的百分率在傷后7d至28d逐漸上升,隨后42d下降。3.(1)小膠質(zhì)細(xì)胞(Iba-l陽(yáng)性)在傷后7d和42d顯著增加。(2)小膠質(zhì)細(xì)胞(Iba-l陽(yáng)性)中,CD86+/CD11b+M1型小膠質(zhì)細(xì)胞在傷后42d表達(dá)顯著增加,CD206+/CD11b+M2型小膠質(zhì)細(xì)胞在傷后7d表達(dá)顯著增加。結(jié)論:1.大鼠rmTBI傷后,存在長(zhǎng)時(shí)程的神經(jīng)行為學(xué)異常和認(rèn)知功能障礙。2.大鼠rmTBI傷后,存在中樞和外周免疫功能的紊亂,其中,慢性期的外周免疫抑制可能對(duì)rmTBI神經(jīng)預(yù)后產(chǎn)生影響。3.大鼠rmTBI傷后,小膠質(zhì)細(xì)胞表型存在一定的變化規(guī)律,急性期以M2型小膠質(zhì)細(xì)胞為主,慢性期以M1型小膠質(zhì)細(xì)胞為主,M1/M2型小膠質(zhì)細(xì)胞的差異表達(dá)可能對(duì)rmTBI的繼發(fā)性損傷產(chǎn)生影響。
[Abstract]:Objective: traumatic brain injury-tibi (TBI) has become the third major disease in the world because of its characteristics of high disability and high mortality, which seriously endangers the health of human beings. In recent years, researchers have paid more and more attention to a neurodegenerative disease called chronic mild traumatic brain encephalopathy, a neurodegenerative disease associated with repeated mild traumatic brain injury-rmTBI, which is common among veterans and rugby players. A boxer, etc At present, the related studies are mainly focused on the behavior and pathology of rmTBI models related to CTE, while the immunological studies of rmTBI models related to CTE have not been reported, which is a blank field of current scientific research. In this study, we first demonstrated the existence of long term neurobehavioral abnormalities and cognitive dysfunction in rmTBI rat model by improved neural function score (mNSS) and Morris water maze test. Secondly, immunofluorescence and flow cytometry were used to study the changes of T cell subsets (CD3 ~ CD4 T cells, CD3 ~ CD8 T cells) and microglial phenotypes (M 1 microglia / M 2 microglia) in rmTBI rats. In order to understand the changes of long term immune response in CTE related rmTBI rat model, to lay the experimental foundation for further exploring its immune mechanism, and to provide the theoretical basis for further exploring the novel immunological prevention and treatment strategy related to CTE. Methods: 1. MNSS and MWM were used to evaluate the neurobehavioral function and cognitive learning level within 42 days after rmTBI injury in rats. The changes of T cell subsets (mainly CD3 ~ CD4 T cells) in brain tissue and peripheral blood of rats after rmTBI injury were detected by flow cytometry. Immunofluorescence and flow cytometry were used to detect the changes of microglial phenotype M 1 microglia type M 2 microglia in rat brain tissue after rmTBI injury for 14 d and 42 d. Results 1. 1 / 1 / 1 / 1 / mNSS showed that there were obvious neurobehavioral abnormalities within 42 days after rmTBI injury in rats. MNSS showed that there was a long term cognitive impairment after rmTBI injury in rats. 2. 1) after rmTBI injury, there was no significant difference between the two groups. The percentage of abnormal T cells with long term central immune function showed a bimodal trend. The percentage of CD3 ~ CD4 T cells in T cells increased significantly at 7 and 42 days after injury, and the percentage of CD3 ~ CD4 T cells in T cells increased 7 days after injury. The percentage of CD3 ~ CD8 T cells in peripheral immunity increased significantly on the 14th day after injury, and the change trend of CD3 ~ CD8 T cells was opposite to that of CD3 ~ CD4 T cells. The percentage of CD3 ~ CD4 T cells in T cells decreased continuously on the 28th day after injury. The percentage of CD3 ~ CD8 T cells in T cells increased gradually from 7 to 28 days after injury. The expression of CD86 / CD11b M1 type microglia was significantly increased on the 42nd day after injury, and the expression of CD206 / CD11b M2 microglia increased significantly on the 7th and 7th day after injury. Conclusion 1. There were long term neurobehavioral abnormalities and cognitive dysfunction after rmTBI injury in rats. There are central and peripheral immune dysfunction after rmTBI injury in rats. The peripheral immunosuppression in chronic phase may affect the prognosis of rmTBI nerve. 3. After rmTBI injury, microglial phenotypic changes were observed in rats. In acute phase, M2 microglia were dominant, and in chronic phase, M1 microglial cells were dominant. The differential expression of M1 / M2 microglia might have an effect on the secondary injury of rmTBI.
【學(xué)位授予單位】：天津醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類(lèi)號(hào)】：R651.15

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本文編號(hào)：1830520