耐甲氧西林金黄色葡萄球菌系统性感染小鼠模型的制备

目的 采用临床分离的耐甲氧西林金黄色葡萄球菌（MRSA）感染ICR小鼠，建立MRSA系统性感染小鼠模型。方法 采用连续3 d腹腔注射环磷酰胺（100 mg/kg）进行免疫抑制后，将浓度为1×10⁷ cfu/mL的MRSA菌液经尾静脉接种ICR小鼠，通过生存分析、外周血白细胞计数、组织载菌量和病理学检查对模型进行评价。结果 MRSA接种后第2天小鼠开始死亡，14 d内累积死亡率达60%；外周血白细胞总数显著升高，细菌在多个器官定植，载菌量由高到低依次是肾、关节、肺、肝和脑，肾载菌量高达10⁹ CFU/g，关节、肺、肝和脑的载菌量范围在10⁴~10⁹ CFU/g。病理观察显示肾、心脏、肺、肝、脑和关节多器官感染的组织病理学改变。结论 采用环磷酰胺免疫抑制后静脉接种MRSA的方法首次成功建立MRSA系统性感染小鼠模型，该模型可应用于MRSA发病机理及药物筛选等研究领域。

Preparation of a mouse model of methicillin-resistant Staphylococcus aureus infection

Objective To establish a mouse model of methicillin-resistant Staphylococcus aureus(MRSA) systemic infection with a MRSA strain isolated from clinical samples. Methods Forty-four ICR mice were randomly divided into experimental group (28 mice) and control group (16 mice). The mice were infected with MRSA (1×10⁷ CFU/mL) by tail vein injection after the mice were treated with cyclophosphamide (100 mg/kg) i.p. for immunosuppression. Survival analysis, peripheral blood white blood cell count, tissue bacterial loads and pathological examination were used to evaluate the models. Results At 2 days after MRSA infection, the treated mice began to die and the cumulative mortality rate reached to 60% at 14 days post-infection. The peripheral blood leukocyte count was significantly increased. MRSA test was positive in the kidneys, joints, lung, liver and brain. The bacterial loads in kidneys reached to 10⁹ CFU/g in joints, lung, liver and brain reached to 10⁴ to 10⁹ CFU/g. Histopathological changes of multiple organ infection were observed in the kidney, heart, lung, liver, brain and joint tissues. Conclusions We have successfully established a mouse model of MRSA systemic infections. It can be a useful model for the study on pathogenesis and new drug development and so on of MRSA infection.