【摘要】：狂犬病(Rabies)是由狂犬病病毒(Rabies virus,RABV)引起的一種高死亡率的人畜共患病,能引起人和其它哺乳動物的大腦炎癥。RABV具有高度的嗜神經(jīng)性,目前人狂犬病病例主要是通過攜帶病毒的犬咬傷傳播。RABV到達(dá)體內(nèi)不會立即傳播,而是在傷口周圍的肌肉組織進(jìn)行復(fù)制,隨后才會進(jìn)入外周神經(jīng)系統(tǒng)并通過神經(jīng)元逆軸突轉(zhuǎn)運(yùn),當(dāng)?shù)竭_(dá)背根神經(jīng)節(jié)后即開始大量增殖并入侵中樞神經(jīng)系統(tǒng)。之后病毒便開始離心性傳播。因此,RABV在中樞神經(jīng)系統(tǒng)逃逸神經(jīng)免疫是引起發(fā)病的重要原因,而目前RABV在中樞神經(jīng)系統(tǒng)逃逸神經(jīng)免疫的機(jī)制尚不清楚。中樞神經(jīng)系統(tǒng)中的固有細(xì)胞以神經(jīng)元和膠質(zhì)細(xì)胞為主。其中小膠質(zhì)細(xì)胞是中樞神經(jīng)系統(tǒng)中的免疫細(xì)胞,也是其內(nèi)最主要的吞噬細(xì)胞,時(shí)刻監(jiān)視著周圍的微環(huán)境,而星形膠質(zhì)細(xì)胞在哺乳動物腦中分布最廣,因此我們把膠質(zhì)細(xì)胞作為研究對象,開展了不同RABV毒株對膠質(zhì)細(xì)胞功能影響的研究。我們以0.01 MOI劑量的RABV固定毒株B2C、野毒株AH08和SX15感染原代培養(yǎng)的混合膠質(zhì)細(xì)胞,檢測了不同病毒在混合膠質(zhì)細(xì)胞中病毒量隨時(shí)間的變化、不同病毒與溶酶體的共定位及對溶酶體功能的影響、不同病毒對小膠質(zhì)細(xì)胞的活化、分型及與神經(jīng)元的互作分子的影響。結(jié)果顯示,RABV固定毒B2C株隨著感染時(shí)間的增加,病毒量先增加后減少,而野毒株AH08病毒量并沒有減少;固定毒B2C株能夠定位到溶酶體中,而野毒株AH08并沒有與溶酶體共定位;與野毒株AH08和SX15相比,固定毒B2C株能夠明顯的活化小膠質(zhì)細(xì)胞并刺激小膠質(zhì)細(xì)胞向抗炎性的小膠質(zhì)細(xì)胞分化;野毒株AH08和SX15能夠刺激小膠質(zhì)細(xì)胞與神經(jīng)元互作的抑制性分子CD172α、CD200R和CX3CR1的表達(dá)。總之,通過研究RABV與膠質(zhì)細(xì)胞之間的作用,初步探索了部分RABV逃逸機(jī)體神經(jīng)系統(tǒng)免疫反應(yīng)的機(jī)制,為RABV的致病機(jī)理研究奠定理論基礎(chǔ),進(jìn)而為狂犬病的防控以及其它狂犬病毒屬病毒的神經(jīng)免疫逃逸機(jī)理研究提供理論依據(jù)。
[Abstract]:Rabies (Rabies) is a kind of high mortality zoonosis caused by Rabies virus, which can cause inflammation in the brain of human and other mammals. At present, human rabies cases are mainly transmitted by bitten dogs carrying the virus. RABV does not spread immediately in the body. Instead, it replicates in the muscle tissue around the wound, and then it enters the peripheral nervous system and is transported through neurons against the axon. When the dorsal root ganglion is reached, it begins to proliferate and invade the central nervous system. The virus then begins to spread centrifugally. The immune mechanism of RABV in central nervous system is still unclear. The intrinsic cells in the central nervous system are mainly neurons and glial cells. Microglia are immune cells in the central nervous system and the most important phagocytes in the central nervous system, monitoring the surrounding microenvironment at all times, while astrocytes are the most widely distributed in the mammalian brain. Therefore, we studied the effects of different RABV strains on glial function. We immobilized the virus strain B2C with the dose of 0.01 MOI RABV, and infected the mixed glial cells with AH08 and SX15 in primary culture. We detected the changes of virus amount in the mixed glial cells with different viruses over time. The co-localization of different viruses with lysosomes and the effects of different viruses on lysosome function, the activation, typing and interaction with neurons of microglia by different viruses. The results showed that with the increase of infection time, the amount of AH08 virus increased first and then decreased, but the amount of AH08 virus did not decrease, the fixed strain B2C could locate in lysosome, but the wild strain AH08 did not co-locate with lysosome. Compared with wild virus strains AH08 and SX15, immobilized B2C strain could activate microglia and stimulate the differentiation of microglia into anti-inflammatory microglia. Wild strain AH08 and SX15 could stimulate the expression of CD172 偽 -CD200R and CX3CR1, which interacted between microglia and neurons. In conclusion, by studying the interaction between RABV and glial cells, the mechanism of immune response of part of RABV to escape nervous system was preliminarily explored, which laid a theoretical foundation for the study of pathogenesis of RABV. It provides a theoretical basis for the prevention and control of rabies and the study of neuroimmune escape mechanism of other rabies viruses.
【學(xué)位授予單位】：華中農(nóng)業(yè)大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：S852.65

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相關(guān)期刊論文 前1條

1 種世桂;趙玉敏;;人狂犬病病例的實(shí)驗(yàn)室診斷技術(shù)及應(yīng)用原則[J];甘肅科技;2016年11期

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