本文關(guān)鍵詞： 狂犬病病毒 細(xì)胞因子 細(xì)胞因子風(fēng)暴　出處：《廣西大學(xué)》2017年碩士論文　論文類型：學(xué)位論文

【摘要】：狂犬病(Rabies)是由狂犬病病毒(Rabies virus)感染引起的一種致死性神經(jīng)性傳染病。能感染包括人在內(nèi)的幾乎所有哺乳動(dòng)物。狂犬病病毒感染宿主主要通過(guò)破損的皮膚或粘膜侵入,臨床大多表現(xiàn)為特異性恐風(fēng)、恐水、咽肌痙攣、進(jìn)行性癱瘓等。近年來(lái),狂犬病報(bào)告死亡數(shù)一直處于我國(guó)法定報(bào)告?zhèn)魅静∏傲?嚴(yán)重影響了人民群眾的生命健康。細(xì)胞因子是由一類低分子量可溶性蛋白質(zhì),由細(xì)胞通過(guò)免疫原、絲裂原或其他因子刺激所產(chǎn)生的,在較低濃度下即可發(fā)揮其生物活性。細(xì)胞因子發(fā)揮作用主要通過(guò)與相應(yīng)受體相互結(jié)合,具有刺激細(xì)胞活化、增殖和分化效應(yīng),調(diào)節(jié)固有免疫和適應(yīng)性免疫應(yīng)答,促進(jìn)造血等功能。細(xì)胞因子風(fēng)暴(cytokine storm),又名高細(xì)胞因子血癥(hypercytokinemia),具體表現(xiàn)為人體受到病毒、細(xì)菌或者納米材料等外界刺激后短時(shí)期內(nèi)產(chǎn)生多種細(xì)胞因子大量持續(xù)性分泌的過(guò)度免疫現(xiàn)象。當(dāng)人體受傷或者感染,首先分泌細(xì)胞因子產(chǎn)生炎癥反應(yīng),激活固有免疫和適應(yīng)性免疫應(yīng)答,并通過(guò)免疫應(yīng)答控制感染。當(dāng)感染受到控制時(shí)細(xì)胞因子及時(shí)恢復(fù)體內(nèi)的動(dòng)態(tài)平衡。然而在某些情況下,這種動(dòng)態(tài)平衡失調(diào),使機(jī)體內(nèi)免疫細(xì)胞被大量活化,進(jìn)而分泌更多的細(xì)胞因子,機(jī)體就會(huì)發(fā)生細(xì)胞因子風(fēng)暴。這對(duì)周圍細(xì)胞所帶來(lái)的損傷可能會(huì)是災(zāi)難性的,甚至?xí)l(fā)死亡。宿主感染狂犬病毒后免疫系統(tǒng)被激活,產(chǎn)生一系列免疫應(yīng)答反應(yīng)。之前研究已證實(shí)狂犬病毒強(qiáng)毒株可以誘導(dǎo)小鼠腦內(nèi)產(chǎn)生高水平IFN-α/β,本研究為了探究狂犬病病毒是否可以誘導(dǎo)小鼠腦內(nèi)產(chǎn)生細(xì)胞因子風(fēng)暴,利用狂犬病病毒固定毒株rRC-HL和廣西代表性街毒強(qiáng)毒分離株GX074以及本實(shí)驗(yàn)室拯救的嵌合重組病毒株rRC-HLAG、rRC-HL△G242-288、Mu11、rRC-HLAG/R333Q對(duì)4周齡昆明小白鼠進(jìn)行腦內(nèi)接毒,采集第4天和第7天腦組織和血清,用ELISA和qPCR的方法檢測(cè)其中各細(xì)胞因子TNF-α、IFN-γ、IL-1β、IL-6、IL-12和MCP-1的濃度及變化量。結(jié)果表明,感染后期狂犬病病毒可以引起小鼠腦內(nèi)產(chǎn)生高水平細(xì)胞因子,并且和病毒毒力以及其引起的臨床癥狀呈正相關(guān)。各病毒株均能引起血清中產(chǎn)生高水平的IL-6,但只有強(qiáng)毒才可以在感染后期刺激血清中產(chǎn)生高水平MCP-1。實(shí)驗(yàn)證實(shí)狂犬病病毒可以引起腦內(nèi)細(xì)胞因子風(fēng)暴,這對(duì)研究狂犬病致病機(jī)理提供了新的思路。
[Abstract]:Rabies is a fatal neurogenic infection caused by rabies virus infection. It can infect almost all mammals, including humans. Rabies virus infects the host mainly by invading through damaged skin or mucous membranes. In recent years, the number of reported deaths from rabies has been in the forefront of reported infectious diseases in China. Cytokines are produced by a class of low molecular weight soluble proteins stimulated by cells through immunogen, mitogen or other factors. Cytokines play a role in stimulating cell activation, proliferation and differentiation, regulating innate and adaptive immune responses, mainly through interaction with the corresponding receptors. Promoting hematopoietic function. Cytokine storm, also known as hypercytokinemia or hypercytokinemia, is characterized by a virus in the human body. After external stimulation such as bacteria or nanomaterials, many kinds of cytokines are produced in a short period of time. When the human body is injured or infected, cytokines are first secreted to produce an inflammatory response. Activate innate and adaptive immune responses, and control infection through immune responses. When infection is controlled, cytokines restore homeostasis in a timely manner. In some cases, however, this imbalance occurs. If the immune cells in the body are activated in large quantities, and more cytokines are released, the body will have a cytokine storm, which can be disastrous to the surrounding cells. It can even lead to death. The host is infected with rabies virus and the immune system is activated. To investigate whether rabies virus can induce cytokine storms in the brain of mice, a series of immune response responses have been established, which have been shown to induce high levels of IFN- 偽 / 尾 in the brain of mice. Rabies virus fixed strain rRC-HL, Guangxi representative street virus isolate GX074 and chimeric recombinant virus strain rRC-HLA G242-288C Mu11rRC-HLAGRC-R333Q were used to inject virus into brain of 4-week-old Kunming mice. Brain tissue and serum were collected on day 4 and day 7, respectively. The concentrations and changes of IL-12 and MCP-1 were detected by ELISA and qPCR. The results showed that rabies virus could induce the production of high level cytokines in the brain of mice. And it was positively correlated with virulence of virus and clinical symptoms. Each strain of virus could produce high level of IL-6 in serum, but only strong virus could produce high level of MCP-1in the serum of late infection. The experiment proved that rabies produced high level of MCP-1.The results showed that rabies produced high level of IL-6 in serum. The disease virus can cause cytokine storms in the brain. This provides a new idea for studying the pathogenic mechanism of rabies.
【學(xué)位授予單位】：廣西大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：S852.65

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