凝血酶原酶基因在小鼠严重急性呼吸综合征肺损伤中的作用

Correlation of fgl2 prothrombinase gene expression with pulmonary impairment in the murine model of severe acute respiratory syndrome

目的:利用鼠肝炎3型病毒(MHV-3)建立小鼠严重急性呼吸综合征(SARS)模型,探讨小鼠fgl2凝血酶原酶基因(mfgl2)与SARS肺损伤,尤其是透明膜和血栓形成之间的关系及其临床意义。方法:Balb/cJ小鼠气管途径感染MHV-3建立小鼠SARS模型,动态观察小鼠一般情况、组织器官的病理学改变及病毒分布情况;免疫组化和原位杂交方法检测其肺组织中mfgl2和纤维蛋白的表达。结果:感染小鼠5 d内死于以肺损伤为主的多器官功能衰竭;肺呈现典型间质性肺炎样改变伴透明膜、血栓形成;所有收集的器官均可检测到病毒的复制;肺支气管浆液腺上皮细胞、间质浸润细胞及肺泡上皮细胞可检测到mfgl2的特异性表达;免疫组化双染色发现肺内透明膜及微血栓形成区域多见mfgl2与纤维蛋白的共沉积。结论:MHV-3诱导的小鼠SARS模型能较好地模拟人类SARS肺损伤的疾病特征,mfgl2在模型肺组织中的特异性高表达可激活凝血酶原,启动局部凝血过程,导致纤维蛋白的沉积,促进肺内血栓和透明膜的形成,提示mfgl2可能是SARS肺损伤又一重要分子机制。

Objective ： To investigate the relationship of murine fibrinogen-like protein 2 （mfgl2） / fibroleukin with pulmonary impairment in the murine model of severe acute respiratory syndrome （SARS）. Methods： The Balb/cJ mice infected with murine hepatitis virus strain 3 （ MHV-3 ） through the trachea were observed for the pathological features and virus distribution in different organs. The expressions of both mfgl2 and fibrino in the lungs were determined by in situ hybridization and immunohistoehemistry. Results： The MHV-3 infected mice developed typical interstitial pneumonia with extensive hyaline membrane formation in the alveoli, presented micro-vascular thrombosis in the pulmonary vessels and died within 5 days. MHV-3 virus replication was identified in all the organs observed. The specific expression of mfgl2 prothrombinase was noted in the terminal and respiratory bronchioles, alveolar epithelia and infiltrating cells. Conclusion ： The characteristics of the pulmonary impairment of SARS in human can be properly simulated by the MHV-3 induced murine model of SARS. The up-regulation of the specific gene mfgl2 in the lungs involved in fibrino deposition and microvascular thrombosis may be largely responsible for SARS-associated pulmonary damages.