耐甲氧西林金黄色葡萄球菌小鼠全身感染模型的建立与评价

Establishment and evaluation of a mouse model of systemic MRSA infection

目的建立稳定、可靠的MRSA全身感染小鼠模型,为MRSA疫苗的研发提供参考依据,并对系统研究MRSA感染的发病机制及其防治策略奠定实验基础。方法在采用国际标准株MRSA-252建立OD600-CFU标准曲线的基础上,经尾静脉注射途径感染BALB/c小鼠,从感染剂量的选择、小鼠的生存率和体重变化、血液及多脏器的细菌定植量以及主要组织器官病理学变化等多个层面进行时相性监测,对建立的小鼠模型进行系统评价。结果经此途径建立的小鼠模型,致死剂量为每只5.0×109CFU,亚致死剂量为每只1.0×109CFU(生存率为60%～70%)。感染后小鼠生存率下降;体重下降;血液及肝脏、脾脏和肾脏均有细菌定植,定植量在感染后第3天达到高峰;心、肝、肺和肾等主要脏器中有较明显的细胞坏死和炎性细胞浸润。结论小鼠模型的建立,将为进一步研究MRSA疫苗的有效性和安全性评价等提供可靠的技术手段。

Objective To establish a stable and reliable mouse model of systemic infection induced by methicillin- resistant Staphylococcus aureus strain 252 （ MRSA-252）, and to provide reference and experimental foundation for the stud- ies on pathogenesis of MRSA infection and development of MRSA vaccine. Methods Based on the establishment of MR- SA-252 OD600-CFU standard curve, BALB/c mice were infected with bacterial suspension via tail vein injection. Then we systematically evaluated the mouse model at different levels, including the selection of infection dose, the survival rate and change of body weight, bacterial number assay of blood samples and major organs, and the histopathological changes among different groups. Results The lethal dose was 5.0 ×109 CFU/mouse and sublethal dose was 1.0 × 109 CFU/mouse, with a survival rate of 60% -70%. It showed a typical manifestation of systemic infection in the mice, including low survival rate, high bacterial load in blood and major organs, with a peak on the 3rd day after infection, and extensive histopathlogi- cal changes including cell death and infiltration of inflammatory cells. Conclusions A mouse model of systemic MRSA in- fection is successfully established. It provides a reliable technical support for efficacy study and safety evaluation of MRSA vaccines.