本文選題：豬鏈球菌 + 溶血素��； 參考：《吉林大學(xué)》2017年碩士論文

【摘要】：豬鏈球菌是一種世界范圍內(nèi)分布的革蘭氏陽(yáng)性機(jī)會(huì)致病菌,也是一種重要的人獸共患病原菌,能導(dǎo)致人和動(dòng)物多種疾病,對(duì)人畜的生命健康均構(gòu)成威脅。在豬群中通常引發(fā)腦炎、肺炎、關(guān)節(jié)炎以及膿毒血癥等疾病,也可以誘發(fā)人的腦膜炎和鏈球菌毒素休克綜合征等多種疾病,嚴(yán)重危害養(yǎng)豬業(yè)的發(fā)展和公眾健康,并且造成巨大的經(jīng)濟(jì)損失。豬鏈球菌成功建立感染的過(guò)程主要包括突破機(jī)體上皮屏障,逃避免疫系統(tǒng)攻擊,在血液中生存和入侵各個(gè)器官,從而擴(kuò)大局部炎癥,這些環(huán)節(jié)都需要豬鏈球菌合成分泌的各種毒力因子介導(dǎo)。豬鏈球菌2型(SS2)表達(dá)分泌多種毒力因子如莢膜多糖、溶血素、溶菌酶釋放蛋白和細(xì)胞外因子等。其中溶血素(Suilysin)是較早確定的豬鏈球菌毒力因子之一,具有細(xì)胞毒性,在豬鏈球菌致病過(guò)程中發(fā)揮重要作用。已有研究報(bào)道分泌溶血素的SS2能穿透人腦微血管內(nèi)皮單層細(xì)胞,并且此生物活性能夠被豬鏈球菌的溶血素抗體所抑制。另外,豬鏈球菌腦膜炎的發(fā)病和流行與其分泌的SLY也有密切關(guān)系。因此,以溶血素為靶標(biāo)可能提供了一種治療豬鏈球菌感染的新思路。本研究根據(jù)SLY表型功能,通過(guò)溶血試驗(yàn)發(fā)現(xiàn)桑色素不影響SLY表達(dá),但可直接中和SLY介導(dǎo)的溶血活性,細(xì)胞感染實(shí)驗(yàn)表明,在豬鏈球菌與宿主細(xì)胞共感染體系內(nèi)加入桑色素可顯著降低細(xì)菌對(duì)細(xì)胞介導(dǎo)的損傷作用,進(jìn)一步提示桑色素是抗豬鏈球菌感染的先導(dǎo)化合物。最后,本實(shí)驗(yàn)建立了豬鏈球菌感染小鼠模型,經(jīng)過(guò)桑色素治療后,感染小鼠腦組織菌落定植數(shù)和死亡率明顯降低。綜上所述,本研究實(shí)驗(yàn)結(jié)果提示桑色素是一種以SLY為靶標(biāo)的抗豬鏈球菌感染的潛在先導(dǎo)化合物,也為臨床研發(fā)抗豬鏈球菌感染新藥提供一定的數(shù)據(jù)和實(shí)驗(yàn)支持。
[Abstract]:Streptococcus suis is a Gram-positive opportunistic pathogen distributed all over the world. It is also an important zoonotic pathogen which can lead to many diseases of human and animal and threaten the life and health of human and animal. In pigs, diseases such as encephalitis, pneumonia, arthritis and sepsis are usually caused, as well as many other diseases, such as meningitis and streptococcal toxin shock syndrome, which are seriously harmful to the development of pig farming and public health. And caused huge economic losses. The successful establishment of infection by Streptococcus suis mainly involves breaking through the epithelial barrier of the body, escaping the attack of the immune system, surviving in the blood and invading various organs, thereby expanding local inflammation. These links require a variety of virulence factors mediated by Streptococcus suis synthesis and secretion. Streptococcus suis type 2 expressed and secreted many virulence factors such as capsule polysaccharide hemolysin lysozyme releasing protein and extracellular factor. Among them, hemolysin (Suilysin) is one of the virulence factors of Streptococcus suis, which has cytotoxicity and plays an important role in the pathogenicity of Streptococcus suis. It has been reported that SS2 secreting hemolysin can penetrate human microvascular endothelial monolayer cells and this biological activity can be inhibited by hemolysin antibody of Streptococcus suis. In addition, the incidence and prevalence of streptococcus suis meningitis is also closely related to SLY secreted by streptococcus suis. Therefore, targeting hemolysin may provide a new idea for the treatment of Streptococcus suis infection. According to the phenotypic function of SLY, the results of hemolysis test showed that Morin did not affect the expression of SLY, but could directly neutralize the hemolytic activity mediated by SLY. Adding Morin into the co-infection system of Streptococcus suis and host cells can significantly reduce the cell mediated damage induced by bacteria, which further indicates that Morin is the leading compound against the infection of Streptococcus suis. Finally, the mice model of streptococcus suis infection was established. After mulberry treatment, the number of colonization and mortality in brain tissue of infected mice were significantly decreased. To sum up, the results of this study suggest that Morin is a potential lead compound against streptococcus suis infection targeting SLY, and also provides some data and experimental support for clinical research and development of new drugs against streptococcus suis infection.
【學(xué)位授予單位】：吉林大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類(lèi)號(hào)】：S858.28

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本文編號(hào)：2026386