MRSA气溶胶诱导烫伤SKH-1无毛小鼠皮肤感染合并肺炎模型

Establishment of a scald SKH-1 hairless mouse model of skin infection combined with pneumonia induced by MRSA aerosol

目的探讨烫伤条件下,建立MRSA气溶胶致SKH-1无毛小鼠皮肤感染合并肺炎模型的方法及其评价指标。方法 48只SKH-1无毛小鼠,随机分成PBS对照组,单纯感染组和烫伤合并感染组。合并感染组小鼠皮肤烫伤后,MRSA(ST-239)气溶胶呼吸道感染,采用体重、血常规、菌血症率、皮肤和脏器荷菌量、病理组织学变化和分子生物学等指标对模型进行综合评价。结果与其他两组相比,合并感染组小鼠第3天体重下降明显;白细胞数显著增多;菌血症率达100%;皮肤和肺荷菌量较高,分别达108CFU/g和106CFU/g;镜下观察皮肤和肺炎症病变明显;免疫组化结果显示皮肤组织内CD138呈阳性表达;multi-PCR测定感染组织内nuc和mecA基因均为阳性。结论 SKH-1无毛小鼠烫伤再辅以MRSA气雾攻击的方式,可成功建立能够模拟临床上烧烫伤患者继发MRSA肺炎的动物模型,此模型对于抗MRSA药物药效评价研究具有重要临床应用价值。

Objective To establish a scald SKH-1 hairless mouse model of skin and lung infection induced by methicillin-resistant Staphylococcus aureus（ MRSA） aerosol and its evaluation criteria. Methods Forty-eight SKH-1 hairless mice were randomly divided into PBS control group,infection group and infection with scald group. After the mouse dorsal skin of the infection with scald group was thermally injured,the mice were challenged with MRSA aerosol（ ST-239）through the respiratory tract. The body weight,blood test,bacteremia rate,skin and organs infection of the model mice were measured,and histopathological observation and multi-PCR for the nuc and mecA genes detection were performed.Results Compared with the other two groups,the infection with scald group had evident weight loss on the third day,remarkable increase of WBC count and a bacteraemia rate of 100%. The number of viable S. aureus in the skin and lungs was 108CFU / g and 106CFU / g,respectively. Inflammatory lesions of the infected tissues were observed under the light microscope. The results of immunohistochemistry showed positive expression of CD138 in the skin,and positive results were also found with both nuc and mecA genes in the mouse infected tissues of the infection with scald group. Conclusions We have successfully established a scald SKH-1 hairless mouse model of skin and lung infection,challenged with MRSA aerosol. This mouse model well simulate clinical burn patients with secondary infection of MRSA pneumonia,and may have important clinical application value for evaluation of MRSA-related antimicrobial treatment.