hACE2转基因小鼠SARS-CoV感染后的病理变化及免疫学反应

Pathological and immunological changes found in SARS-CoV infected hACE2 transgenic mice

目的观察SARS-CoV感染人血管紧张素转换酶2(hACE2)转基因小鼠引起的病理变化并初步探讨其发生的免疫学机制,为SARS研究提供可靠的动物模型。方法实时PCR测定hACE2转基因小鼠的拷贝数;用PUMC01株SARS-CoV感染hACE2转基因小鼠,光镜下观察小鼠全身组织器官的病理变化;ELISA方法检测血清特异性抗体和肺组织匀浆上清细胞因子TNF-α、IL-6、IFN-γ变化。结果单拷贝hACE2转基因小鼠在感染SARS-CoV后肺组织出现更严重的间质性肺炎并伴有肺外多器官损伤;少数转基因小鼠血清检测到特异性IgG抗体;转基因小鼠肺组织匀浆上清TNF-α、IL-6、IFN-γ的水平明显升高。结论hACE2转基因小鼠感染SARS-CoV后出现与人类SARS患者相似的病理特征和免疫学反应,为研究SARS发病机制和药物评价提供了小动物模型。

Objective To establish a sensitive animal model of SARS, we studied the pathological and immunological changes from SARS-CoV infected human angiotensin-converting enzymez （hACE2） transgenic mice. Methods After copy number of hACE2 transgenic mice was determined by Real-time PCR, the animals were infected with PUMC01 strain of SARS-CoV through nasal cavity. The systemic pathological changes were observed by microscopey. The specific antibodies in serum and cytokines of TNF-α, IL-6 and IFN-γ in the superuatant of lung ho- mogenates were detected by ELISA. Results The hACE2 transgenic mice with a single copy showed more severe interstitial pneumonia accompanied by multiple extra-pulmonary organ damages. The specific antibody was found in a few of transgenic mice. Levels of TNF-α, IL-6 and IFN-γ in the supernatant of lung homogenates from transgenic mice were increased more markedly after inoculation of SARS-CoV. Conclusion Like human SARS case, the hACE2 transgenic mice infected by SARS-CoV had similar pathological and immunological changes. This animal model can be used to study pathogenesis of SARS and evaluate the effect of anti-SARS-CoV drugs.