密度感应系统对铜绿假单胞菌致病力及生物被膜形成影响的实验研究

发布时间：2018-01-31 06:22

本文关键词： 铜绿假单胞菌生物被膜密度感应系统聚维酮碘　出处：《吉林大学》2008年博士论文　论文类型：学位论文

【摘要】： 铜绿假单胞菌(Pseudomonas aeruginosa,PAO)是临床上最常见的引起严重医院内获得性感染的条件致病菌。在人体抵抗力低下时容易引起慢性感染,由PAO引起的医院内感染高达30%以上,临床上常见一些慢性创面久治不愈,如皮肤溃疡、褥疮、烧伤感染及糖尿病足等的感染终末菌均为铜绿假单胞菌,增加了患者的负担。一部分因为细菌生物被膜的形成,另一原因为细菌调节宿主炎症反应及免疫反应,改变宿主的免疫监视功能,从而产生很强的耐药性。国内外研究者考虑能否通过减低细菌毒力的方法达到控制感染的目的,最近发现细菌自身密度感应系统(quorum sensing QS)在铜绿假单胞菌致病因子的表达、抗生素的敏感性以及生物被膜分化及形成上起着至关重要的作用;而且发现这种自身诱导分子对机体内的细胞也有不同程度的影响,调节机体的炎症反应及免疫应答。然而在皮肤组织内关于生物被膜形成的研究报道很少,本实验建立大鼠铜绿假单胞菌皮肤感染模型,从形态学角度观察到在大鼠溃疡面于细菌接种8小时开始形成生物被膜;同时为了观察QS系统对大鼠皮肤感染及生物被膜形成的影响,我们建立野生型铜绿假单胞菌(PAO1)及遗传子缺陷的变异菌株(不含LasI及RhlI基因)的大鼠溃疡感染模型,结果发现铜绿假单胞菌感染大鼠皮肤后,在第1、3、7天突变株生物被膜明显较野生型薄,组织内细菌寄生能力弱。生物被膜是细菌的耐药机制之一,临床上没有针对生物被膜有效的治疗方法,我们采用含有脂质的聚维酮碘凝胶应用在感染了铜绿假单胞菌的大鼠创面,结果发现该消毒药可以明显减少生物被膜的形成,促进创面上皮化,是一个可以开发的新型消毒药剂型。
[Abstract]:Pseudomonas aeruginosa. Pao) is the most common opportunistic bacteria causing severe nosocomial infection in clinic. It is easy to cause chronic infection when human body resistance is low. The nosocomial infection caused by PAO is more than 30%. It is common in clinic that some chronic wounds can not be cured for a long time, such as skin ulcer, bedsore, burn infection and diabetic foot infection, all of which are Pseudomonas aeruginosa. It increases the burden of patients, partly because of the formation of bacterial biofilm, and partly because bacteria regulate the inflammation and immune response of the host, and change the immune surveillance function of the host, thus producing strong drug resistance. Researchers at home and abroad consider whether it is possible to control infection by reducing bacterial virulence. The expression of quorum sensing QS in Pseudomonas aeruginosa was recently found. The sensitivity of antibiotics and the differentiation and formation of biofilm play an important role. It is also found that the self-induced molecules have different effects on the cells in the body, and regulate the inflammatory response and immune response of the body. However, there are few reports on biofilm formation in skin tissue. In this study, the skin infection model of Pseudomonas aeruginosa was established in rats. From the morphological point of view, the biofilm was observed on the ulcer surface of rats at 8 hours after inoculation. In order to observe the effect of QS system on skin infection and biofilm formation in rats. We established a rat model of ulcer infection of wild Pseudomonas aeruginosa (PAO1) and mutant strains with genetic defects (excluding LasI and RhlI genes). The results showed that the biofilm of Pseudomonas aeruginosa infected rat skin was thinner than that of wild type on the 1st day of 3rd day, and the parasitic ability of bacteria in the tissue was weak. Biofilm is one of the drug resistant mechanisms of bacteria. There is no effective treatment for biofilm in clinic. We used povidone iodine gel containing lipid in the wound of rats infected with Pseudomonas aeruginosa. The results showed that the disinfectant can obviously reduce the formation of biofilm and promote wound epithelization. It is a new type of disinfectant that can be developed.
【学位授予单位】：吉林大学
【学位级别】：博士
【学位授予年份】：2008
【分类号】：R378

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