基础医学与临床 ›› 2008, Vol. 28 ›› Issue (6): 595-599.

• 研究论文 • 上一篇    下一篇

人ACE2转基因小鼠SARS-CoV感染后的病理变化及免疫学反应

杨秀红 陈云新 朱华 黄澜 马春梅 刘亚莉 秦川   

  1. 华北煤炭医学院生理学教研室 中国医学科学院 中国协和医科大学 实验动物研究所 中国医学科学院 中国协和医科大学 实验动物研究所 中国医学科学院 中国协和医科大学 实验动物研究所 中国医学科学院 中国协和医科大学 实验动物研究所 中国医学科学院 中国协和医科大学 实验动物研究所 中国医学科学院 中国协和医科大学 实验动物研究所
  • 收稿日期:2001-09-12 修回日期:2007-11-29 出版日期:2008-06-25 发布日期:2008-06-25
  • 通讯作者: 杨秀红

Pathological and immunological changes on SARS-CoV infected human ACE2 transgenic mice

Xiu-hong YANG, Yun-xin CHEN, Hua ZHU, Lan LAN, Chun-mei MA, Ya-li LIU, Chuan QIN   

  1. 1 Chinese Academy of Medical sciences & Pejing Uion Medical College,Institute of laboratory Animal Science, Bejing, China, 100021
  • Received:2001-09-12 Revised:2007-11-29 Online:2008-06-25 Published:2008-06-25
  • Contact: Xiu-hong YANG,

摘要: 目的:观察SARS-CoV感染人血管紧张素转换酶2(ACE2)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测定人ACE2转基因小鼠的拷贝数;用PUMC01株SARS-CoV感染ACE2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:单拷贝人ACE2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:人ACE2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。

关键词: 血管紧张素转换酶2, 转基因小鼠, SARS, 病理学, 免疫学

Abstract: Objective To establish susceptible animal model of SARS, we studied the pathological and immunological changes on SARS-CoV infected human ACE2 mice. Methods After copy number of human ACE2 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 under microscope. The specific antibodies in serum and cytokines of TNF-α, IL-6 and IFN-γ in the supernatant of lung homogenates were detected by ELISA. Results The human ACE2 transgenic mice with a single copy showed more severe interstitial pneumonia accompanied by many 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 they were inoculated with SARS-CoV. Conclusion Resembling human SARS case, the human ACE2 transgenic mice with infected by SARS-CoV had similar pathological and immunological changes. This small animal model can be used to study pathogenesis of SARS and evaluate the effect of anti-SARS-CoV drugs.

Key words: angiotensin-converting enzyme 2, transgenic mice, severe acute respiratory syndrome, pathology, immunology