A study of idopathic interstitial pneumonia with transgenic mouse (HCV)

IPF（间质性肺纤维化）的发病机制尚不清楚，但其预后较差.我们推测，HCV作为肝纤维化的主要病原体之一，可能在IIP中发挥作用。首先，我们证实了IPF患者在更大的人群中具有抗HCV抗体，并且与对照组相比，在HCV的RT-PCR中更频繁地呈阳性。在这项研究中，我们使用HCV转基因小鼠研究了这种病毒在IPF中的作用。在HCV转基因小鼠中，少量二氧化硅（如8 mg）在肺中观察到显著的严重纤维化改变。促炎细胞因子如IGF-1和TGF-β在肺中以剂量依赖性方式响应二氧化硅而增加，但在转基因和非转基因小鼠之间未观察到显著差异。另一方面，与对照相比，HCV转基因小鼠具有显著高的IL-4和INF-γ的mRNA表达。这些结果表明，HCV可能促进了肺纤维化的进展，响应于二氧化硅与不同的细胞因子谱。

Pathogenesis of IPF (interstitial pulmonary fibrosis) is still unclear despite of its poor prognosis. We hypothesized that HCV, which has been recognized, as one of major pathogen of fibrous change in liver, may play a role in IIP. First, we confirmed patients with IPF have antibody against HCV in a larger population and are more frequently positive in RT-PCR to HCV as compared to controls. In this study we investigated the role of this virus in IPF using the HCV transgenic mouse. In HCV transgenic mouse significantly sever fibrous changes were observed in lung with a small amount of silica such as 8 mg. Pro-inflammatory cytokines such as IGF-1 and TGF-beta increased in the lung in response to silica in a dose dependent manner but no significant differences were observed between transgenic and non-transgenic mouse. On the other hand, HCV transgenic mouse had significantly high expression of mRNA of IL-4 and INF-gamma as compared to controls. These findings proposed that HCV might promote the progression of fibrous changes in lung in response to silica with different profiles of cytokines.