本文選題：反復輕度腦創(chuàng)傷 + 神經行為學　； 參考：《天津醫(yī)科大學》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,嚴重危害著人類的健康,已成為全世界第三大疾病。近年來,一種與反復輕度腦創(chuàng)傷(repetitive mild traumatic brain injury,rmTBI)相關的神經退行性疾病——慢性創(chuàng)傷性腦病(chronic traumatic encephalopathy,CTE)得到了研究學者們越來越多的關注,該疾病常見于退伍士兵、橄欖球運動員、拳擊選手等�，F階段,相關研究主要集中于CTE相關的rmTBI模型中行為學和病理學的研究,而CTE相關的rmTBI模型的免疫學研究尚未報道,屬于目前科學研究的空白領域。本實驗首先通過改進的神經功能評分(mNSS)和Morris水迷宮實驗(MWM),證實rmTBI大鼠模型存在長時程的神經行為學異常和認知功能障礙,其次運用免疫熒光術和流式細胞術初步研究rmTBI大鼠模型中T細胞亞群(CD3~+T細胞、CD3~+CD4+T細胞、CD3~+CD8+T細胞)以及小膠質細胞表型(M1型小膠質細胞、M2型小膠質細胞)的變化規(guī)律,以了解CTE相關rmTBI大鼠模型中長時程免疫反應的變化規(guī)律,為進一步探索其免疫機制奠定實驗基礎,同時也為進一步探討CTE相關的新穎免疫防治策略提供理論依據。研究方法:1.mNSS和MWM評價大鼠rmTBI傷后42d內的神經行為學功能和認知學習水平。2.應用流式細胞儀檢測大鼠rmTBI傷后腦組織以及外周血中1d、3d、7d、14d、28d以及42d的T細胞亞群(主要集中在CD3~+T細胞、CD3~+CD4+T細胞、CD3~+CD8+T細胞)的變化規(guī)律。3.應用免疫熒光、流式細胞儀檢測大鼠rmTBI傷后腦組織中7d、14d、28d及42d的小膠質細胞表型(M1型小膠質細胞、M2型小膠質細胞)的變化規(guī)律。結果:1.(1)mNSS表明,大鼠rmTBI傷后42d內存在明顯的神經行為學異常。(2)MWM表明,大鼠rmTBI傷后存在長時程的認知功能障礙。2.(1)大鼠rmTBI傷后,存在長時程中樞免疫功能的異常,T細胞(CD3~+T細胞)百分率呈雙峰型趨勢,在7d和42d顯著上升。T細胞中CD3~+CD4+T細胞的百分率在傷后7d上升,之后持續(xù)下降。T細胞中CD3~+CD8+T細胞的變化趨勢恰與CD3~+CD4+T細胞的變化趨勢相反。(2)外周免疫中,T細胞(CD3~+T細胞)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細胞中CD3~+CD4+T細胞的百分率在傷后持續(xù)下降。T細胞中CD3~+CD8+T細胞的百分率在傷后7d至28d逐漸上升,隨后42d下降。3.(1)小膠質細胞(Iba-l陽性)在傷后7d和42d顯著增加。(2)小膠質細胞(Iba-l陽性)中,CD86+/CD11b+M1型小膠質細胞在傷后42d表達顯著增加,CD206+/CD11b+M2型小膠質細胞在傷后7d表達顯著增加。結論:1.大鼠rmTBI傷后,存在長時程的神經行為學異常和認知功能障礙。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rmTBI神經預后產生影響。3.大鼠rmTBI傷后,小膠質細胞表型存在一定的變化規(guī)律,急性期以M2型小膠質細胞為主,慢性期以M1型小膠質細胞為主,M1/M2型小膠質細胞的差異表達可能對rmTBI的繼發(fā)性損傷產生影響。
[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.
【學位授予單位】：天津醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R651.15

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本文編號：1830520