桑色素对猪链球菌溶血素抑制作用的研究

发布时间：2018-06-16 10:43

本文选题：猪链球菌 + 溶血素　；参考：《吉林大学》2017年硕士论文

【摘要】：猪链球菌是一种世界范围内分布的革兰氏阳性机会致病菌,也是一种重要的人兽共患病原菌,能导致人和动物多种疾病,对人畜的生命健康均构成威胁。在猪群中通常引发脑炎、肺炎、关节炎以及脓毒血症等疾病,也可以诱发人的脑膜炎和链球菌毒素休克综合征等多种疾病,严重危害养猪业的发展和公众健康,并且造成巨大的经济损失。猪链球菌成功建立感染的过程主要包括突破机体上皮屏障,逃避免疫系统攻击,在血液中生存和入侵各个器官,从而扩大局部炎症,这些环节都需要猪链球菌合成分泌的各种毒力因子介导。猪链球菌2型(SS2)表达分泌多种毒力因子如荚膜多糖、溶血素、溶菌酶释放蛋白和细胞外因子等。其中溶血素(Suilysin)是较早确定的猪链球菌毒力因子之一,具有细胞毒性,在猪链球菌致病过程中发挥重要作用。已有研究报道分泌溶血素的SS2能穿透人脑微血管内皮单层细胞,并且此生物活性能够被猪链球菌的溶血素抗体所抑制。另外,猪链球菌脑膜炎的发病和流行与其分泌的SLY也有密切关系。因此,以溶血素为靶标可能提供了一种治疗猪链球菌感染的新思路。本研究根据SLY表型功能,通过溶血试验发现桑色素不影响SLY表达,但可直接中和SLY介导的溶血活性,细胞感染实验表明,在猪链球菌与宿主细胞共感染体系内加入桑色素可显著降低细菌对细胞介导的损伤作用,进一步提示桑色素是抗猪链球菌感染的先导化合物。最后,本实验建立了猪链球菌感染小鼠模型,经过桑色素治疗后,感染小鼠脑组织菌落定植数和死亡率明显降低。综上所述,本研究实验结果提示桑色素是一种以SLY为靶标的抗猪链球菌感染的潜在先导化合物,也为临床研发抗猪链球菌感染新药提供一定的数据和实验支持。
[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.
【学位授予单位】：吉林大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：S858.28

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