Murine gammaherpes virus as a cofactor in the development of pulmonary fibrosis in bleomycin resistant mice
Murine gammaherpes virus as a cofactor in the development of pulmonary fibrosis in bleomycin resistant mice
复制标题
DOI：
10.1183/09031936.02.00272902
复制
发表时间：
2002-11-01
影响因子：
24.3
通讯作者：
Egan, JJ
中科院分区：
文献类型：
--
作者：
Lok, SS;Haider, Y;Egan, JJ
对人体组织的研究表明，产生性Epstein Barr病毒与特发性肺纤维化(IPF)之间存在关联。然而，该病毒的致病作用尚未确定。本研究旨在建立一种探讨病毒感染与肺纤维化之间关系的动物模型。对博莱霉素耐药的BALB/c小鼠(n=30)，用小鼠伽玛疱疹病毒68免疫小鼠，然后腹腔注射博莱霉素。博莱霉素治疗28天后处死小鼠，进行肺组织学和生化检测。BALB/c小鼠接受病毒和博莱霉素组的肺纤维化(中位数为2.2分)高于仅接受博莱霉素组(中位数为0)、单纯病毒组(中位数为0.2)或磷酸盐缓冲盐水(PBS)对照组(中位数0)。同样，与博莱霉素组(中位数0.5)、病毒组(中位数0.8)或PBS对照组(中位数0.2)相比，同时接受病毒和博莱霉素组的小鼠表现出更多的肺部炎症(中位数评分1.9)。博莱霉素组和病毒组的胶原含量(平均1.86 mg)与白霉素组(平均L 2 mg)相比差异有统计学意义，提示病毒单独作用不会导致肺纤维化，但在外源性损伤的情况下复制病毒可能会促进肺纤维化的发展。
Studies of human tissue have suggested an association between productive Epstein Barr virus and idiopathic pulmonary fibrosis (IPF). However, a pathogenic role for the virus has not been established. This study was undertaken to develop an animal model, which would explore the association between viral infection and pulmonary fibrosis.BALB/c mice (n=30), resistant to bleomycin, were primed with murine gammaherpesvirus 68 and then given intraperitoneal bleomycin. The mice were sacrificed at 28 days after bleomycin and their lungs assessed histologically and biochemically. Lung pathology was scored 0-3 for fibrotic and inflammatory change.BALB/c mice given virus and bleomycin showed more lung fibrosis (median score 2.2) compared to those given bleomycin alone (median 0), virus alone (median 0.2) or phosphate-buffered saline (PBS) control (median 0). Similarly mice given both virus and bleomycin showed more lung inflammation (median score 1.9) compared to those given bleomycin (median 0.5), virus (median 0.8), or PBS control (median 0.2). There was a significant difference in collagen content between the bleomycin and virus group (mean 1.86 mg) compared to the belomycin alone group (mean L 2 mg).These results suggest that virus alone does not result in pulmonary fibrosis but that replicating virus in the presence of an exogenous injury may promote the development of pulmonary fibrosis.