β2-受体阻滞剂ICI118551调控绿脓杆菌VI型分泌系统抑制角膜感染的机制研究

绿脓杆菌性角膜炎是由绿脓杆菌感染引起的严重化脓性角膜炎，发病迅速，是发展中国家主要致盲性眼病之一。前期研究我们发现，选择性β2-肾上腺素受体阻滞剂ICI118551可显著抑制小鼠绿脓杆菌性角膜炎的发生发展，主要表现为减少角膜中的细菌载量和毒力因子的分泌以及中性粒细胞的浸润。体外细菌培养实验证明ICI118551对绿脓杆菌有较强的杀菌能力，进一步转录组测序分析显示，在ICI118551的作用下，细菌有“抗菌活性”的VI型分泌系统（T6SS）相关基因表达大幅上调。在此研究基础上，本项目拟利用小鼠角膜绿脓杆菌感染模型，结合P. aeruginosa 19660 T6SS敲除菌株，深入探究T6SS在绿脓杆菌角膜感染过程中所起的作用，以及ICI118551通过紊乱细菌T6SS功能而对绿脓杆菌造成杀灭作用的抗菌机制，为绿脓杆菌性角膜炎的临床治疗提供新的研究思路和干预靶点。

Pseudomonas aeruginosa keratitis is a serious suppurative keratitis caused by P. aeruginosa infection. It is one of the main blinding eye diseases in developing countries. In the previous study, we found that the selective β 2-adrenergic receptor blocker ICI118551 could significantly inhibit the development of P. aeruginosa keratitis in mice, which is mainly manifested in the reduction of bacterial load, the secretion of virulence factors and the infiltration of neutrophils. In vitro bacterial culture experiments showed that ICI118551 had strong antibacterial ability against P. aeruginosa. Further analysis of transcriptome sequencing showed that ICI118551 significantly increased the expression of genes related to the type VI secretion system of bacteria with "antibacterial activity". On the basis of this data, this study intends to use the mouse corneal P. aeruginosa infection model, combined with P. aeruginosa 19660 T6SS knock-out mutants, to further explore the role of T6SS played during the process of P. aeruginosa corneal infection, and the inhibition mechanism of ICI118551 on P. aeruginosa keratitis mediated by T6SS, providing new research ideas and intervention targets for the clinical treatment of P. aeruginosa keratitis.