Toll样受体3介导呼吸道合胞病毒感染的炎症反应

发布时间：2018-01-19 05:25

本文关键词： Toll样受体3 呼吸道合胞病毒核转录因子κB 肿瘤坏死因子α　出处：《安徽医科大学》2007年硕士论文　论文类型：学位论文

【摘要】： 呼吸道合胞病毒(respiratory syncytial virus,RSV)为副粘病毒科肺炎病毒属,是有包膜非节段性的单负链RNA病毒,是世界范围内婴幼儿病毒性下呼吸道感染最重要的病毒病原,人们也越来越认识到呼吸道合胞病毒是中老年和免疫缺陷成年人呼吸道感染的重要病毒性病原。病毒通过细胞融合侵入呼吸道上皮,能诱导宿主表达和分泌大量的促炎性因子和免疫调节分子。严重的RSV感染包括炎症介质的释放、上皮细胞坏死、炎症的发生、大量粘液的产生等,新近发现的Toll样受体,为研究RSV感染的炎症反应机理提供了新的思路。Toll样受体(Toll-like receptors,TLRs)为I型跨膜蛋白,是识别病原体的重要受体,它们识别细菌、病毒或环境中的配体,启动天然免疫反应和调节获得性免疫反应。研究发现TLR3(Toll-like receptor 3)能特异性地识别双链RNA(大多数病毒在复制和转录过程中均可合成), TLR3介导的信号转导通路参与激活呼吸道上皮细胞,分泌大量炎症免疫相关细胞因子,在呼吸道合胞病毒感染引起肺炎的发生发展过程中发挥重要作用。呼吸道合胞病毒感染的机制十分复杂,目前尚不清楚,也无理想的治疗药物和疫苗。因此,深入研究RSV感染的分子机制具有重要医学意义。目的:研究呼吸道合胞病毒感染后TLR3的表达变化;探讨TLR3介导RSV感染的炎性反应及其部分信号转导通路。方法:用RSV分别于体外感染A549细胞和体内滴鼻感染昆明小鼠,取不同感染时间点的A549细胞和小鼠肺,用半定量逆转录聚合酶链反应检测TLR3和TNF-αmRNA的表达变化,用免疫印迹法检测TLR3蛋白和核内活性NF-κBp65蛋白的表达变化,用酶联免疫法检测细胞培养上清和小鼠血清中的TNF-α表达变化。结果:RSV感染上调TLR3 mRNA和TNF-αmRNA的转录水平;诱导活化核内NF-κBp65蛋白的表达;升高细胞培养上清和小鼠血清中TNF-α的分泌量。各指标的变化较对照组均有显著性差异。结论:呼吸道合胞病毒感染可以上调TLR3mRNA的表达,病毒诱导的炎症反应与TLR3介导的信号转导途径有关,TLR3介导NF-κB的活化,促使TNF-α过度表达释放。表明TLR3确实参与了RSV诱导的炎症反应。
[Abstract]:Toll - like receptor ( TLRs ) is one of the most important viral pathogens . Toll - like receptor ( TLRs ) is an important receptor to identify pathogens . Toll - like receptor ( TLRs ) is an important receptor to identify pathogens . Toll - like receptor ( TLRs ) is an important receptor to identify pathogens . Toll - like receptor ( TLRs ) is an important receptor for studying the pathogenesis of RSV infection . Objective : To investigate the expression of TLR3 in RSV infection and to investigate the inflammatory response and partial signal transduction pathways of TLR3 - mediated RSV infection . Methods : The expression of TLR3 and TNF - 伪 mRNA was detected by semi - quantitative reverse transcription polymerase chain reaction ( RT - PCR ) , and the expression of TLR3 and TNF - 伪 mRNA was detected by semi - quantitative reverse transcription polymerase chain reaction ( RT - PCR ) . Results : The level of TLR3 mRNA and TNF - 伪 mRNA was up - regulated by RSV infection , and the expression of NF - 魏B P65 protein was induced by RSV infection , and the secretion of TNF - 伪 was increased in the supernatant and serum of mice . Conclusion : Respiratory Syncytial Virus Infection can up - regulate the expression of TLR3 mRNA . The inflammatory response induced by the virus is related to TLR3 - mediated signal transduction pathway . TLR3 - mediated NF - 魏B activation promotes the release of TNF - 伪 . It is shown that TLR3 is indeed involved in RSV - induced inflammatory response .

【学位授予单位】：安徽医科大学
【学位级别】：硕士
【学位授予年份】：2007
【分类号】：R363

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