本文關(guān)鍵詞：鼠疫耶爾森氏菌和宿主相互作用的體內(nèi)轉(zhuǎn)錄譜研究　出處：《中國人民解放軍軍事醫(yī)學(xué)科學(xué)院》2007年博士論文　論文類型：學(xué)位論文

  更多相關(guān)文章： 鼠疫耶爾森氏菌 肺鼠疫 芯片 組織病理學(xué) 體內(nèi)轉(zhuǎn)錄譜

【摘要】： 鼠疫耶爾森氏菌(以下簡稱鼠疫菌)是鼠疫的病原體，，主要引發(fā)三種類型的鼠疫：腺鼠疫、肺鼠疫和敗血癥型鼠疫。肺鼠疫具有傳染性強(qiáng)和致死率高的特點(diǎn)。在自然界中，鼠疫菌通常在嚙齒類動物和跳蚤間相互傳播并進(jìn)行保存；因此鼠疫菌在其生活周期中要適應(yīng)跳蚤前胃以及嚙齒動物體內(nèi)的微環(huán)境變化(溫度、pH值、離子強(qiáng)度等)才能生存。鼠疫菌利用復(fù)雜高效的轉(zhuǎn)錄調(diào)控機(jī)制來應(yīng)對這種環(huán)境條件的劇烈變化，實(shí)現(xiàn)其傳播和致病能力。 感染性疾病的發(fā)生實(shí)際上是病原體與宿主相互作用的一個互動過程。在此期間，既有病原體為逃避宿主防御機(jī)制而進(jìn)行的改變，也有宿主為清除病原體而調(diào)動防御體系的努力。本課題通過建立小鼠經(jīng)鼻內(nèi)感染鼠疫菌的動物模型，模擬鼠疫菌在自然感染過程中經(jīng)歷的溫度改變及氣溶膠傳播的過程；在感染后不同時間點(diǎn)進(jìn)行病理學(xué)觀察；利用逆轉(zhuǎn)錄-定量PCR技術(shù)研究鼠疫菌重要基因(毒力因子、整體調(diào)控因子、轉(zhuǎn)錄因子、雙組分調(diào)控系統(tǒng)、密度感應(yīng)系統(tǒng)等)在致病過程中的轉(zhuǎn)錄變化；并利用芯片技術(shù)研究感染過程中小鼠的全局性轉(zhuǎn)錄組學(xué)變化。 本研究首先建立了肺鼠疫的動物感染模型，并獲得了鼠疫感染過程中的系統(tǒng)病理學(xué)資料，結(jié)果顯示鼠疫菌感染在宿主體內(nèi)呈現(xiàn)典型的肺鼠疫發(fā)展過程，根據(jù)肺組織的病理學(xué)變化將感染分為三個時期：早期、中期和晚期。鼠疫菌的轉(zhuǎn)錄譜數(shù)據(jù)提供了鼠疫菌部分調(diào)控基因在體內(nèi)的轉(zhuǎn)錄動態(tài)變化；確定了不同感染時期和不同組織中調(diào)控基因的轉(zhuǎn)錄差異變化；并與體外(26℃)轉(zhuǎn)錄水平進(jìn)行比較，對鼠疫菌重要基因在感染過程中發(fā)生的轉(zhuǎn)錄調(diào)節(jié)進(jìn)行分析，初步探討這些基因在鼠疫菌致病過程中發(fā)揮的作用及可能參與的機(jī)制。小鼠的全局性轉(zhuǎn)錄組數(shù)據(jù)顯示肺鼠疫早期和晚期及不同組織小鼠具有不同的基因表達(dá)模式；感染晚期大量基因發(fā)生轉(zhuǎn)錄調(diào)節(jié)，并表現(xiàn)為全局性轉(zhuǎn)錄下調(diào)。綜合上述結(jié)果，初步分析了小鼠肺鼠疫發(fā)展過程中，組織病理學(xué)改變與鼠疫菌基因以及宿主相應(yīng)基因的轉(zhuǎn)錄變化之間的相關(guān)性；初步探討了鼠疫菌部分調(diào)控基因在感染過程中發(fā)揮的作用及可能參與的致病機(jī)制；并在轉(zhuǎn)錄水平上從宿主和病原體相互作用的角度探究鼠疫菌的致病機(jī)制。
[Abstract]:Jerson S (hereinafter referred to as the plague bacterium Yersinia pestis) is the pathogen of plague, the plague caused mainly three types: bubonic plague, pneumonic and septicemic plague. Pneumonic plague is contagious and strong death rate is high. In nature, usually in rodent animal plague and flea transmitted and saved; therefore, Yersinia pestis in the life cycle to adapt to the stomach in rodents and flea micro environmental changes (temperature, pH value, ionic strength etc.) to survive. Dramatic changes in the mechanism of transcriptional regulation of Yersinia pestis by complex and efficient to deal with the environmental conditions, the propagation and pathogenicity.
The occurrence of infectious diseases is actually a process of interaction between pathogen and host interaction. During this period, both pathogens to evade host defense mechanisms of change, also have to clear the pathogen and the host defense system to mobilize efforts. This paper through the establishment of the animal model of mice infected with plague bacteria in the nose, process temperature and the change of aerosol transmission simulation experience in Yersinia pestis during natural infection; the pathologic changes were observed in different time after infection; using reverse transcriptase quantitative PCR of Yersinia pestis gene (an important virulence factor, the overall regulatory factor, transcription factor, two-component regulatory system, quorum sensing system) changes in transcription in the pathogenic process; and the global transcriptome microarray in mice during infection changes.
This research has established the pneumonic plague infected animal model and obtain the system in the process of plague infection pathological data, results show that the typical development process in the host of pneumonic plague bacteria infection, according to the pulmonary pathological changes of infection will be divided into three periods: early, middle and late data. Provides some regulatory genes in Yersinia pestis transcription in vivo transcription dynamics of plague bacteria spectrum; determine the changes of transcription regulation differences in different infection stages and different tissues and in vitro gene; and (26 C) compared to the level of transcription, transcription of important gene of Yersinia pestis in the infection process regulation analysis, preliminary to explore the mechanism of these genes play in the pathogenesis of Y.pestis in effect and may be involved in mice. The global transcriptome data show that early and late lung plague in different tissues and small Rats with different patterns of gene expression; gene transcription occurs late a lot of infection, and the performance for the global transcription down. From the above results, a preliminary analysis of the plague in mice in the process of development, change and correlation between transcriptional changes of Yersinia pestis genes and the corresponding genes of host tissue pathology; preliminary study on pathogenic mechanism play a part regulation of gene of Yersinia pestis role during infection and may be involved in the pathogenesis of; and at the level of transcription from the host pathogen interaction perspective of Yersinia pestis.

【學(xué)位授予單位】：中國人民解放軍軍事醫(yī)學(xué)科學(xué)院
【學(xué)位級別】：博士
【學(xué)位授予年份】：2007
【分類號】：R378

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