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

转基因小鼠（HCV）特发性间质性肺炎的研究

• 批准号: 13670617
• 负责人: NAKANO Junichi
• 金额: $ 2.62万
• 依托单位: Teikyo University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13670617/
• 关键词: pulmonary fibrosis; mouse; hepatitis C virus; transgenic; cytokine; apoptosis; IL-4; interstitial pneumonia; 肺繊維症; HCV; シリカ; トランスジェニック; PDGF; 肝炎; ウイルス

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.

尽管预后不佳，但IPF（间质性肺纤维化）的发病机制仍不清楚。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。

项目成果

中野 純一: "HCVトランスジェニックマウスによる間質性肺炎の検討"日本呼吸器学会雑誌. 41. 86 (2003)

Junichi Nakano：“HCV 转基因小鼠间质性肺炎的研究”日本呼吸学会杂志 41. 86 (2003)。

J Nakano et al.: "HCV promotes fibrosis in lung via inhibition of apoptosis in murine model."in mannscript.

J Nakano 等人：“在小鼠模型中，HCV 通过抑制细胞凋亡促进肺纤维化”，参见 mannscript。

J Nakano, N Yamashita, K Ohta: "HCV promotes fibrosis in lung via inhibition of apoptosis in murine model"American Journal of Respiratory Cell and Molecular Biology. (in manuscript).

J Nakano、N Yamashita、K Ohta：“HCV 在小鼠模型中通过抑制细胞凋亡促进肺纤维化”《美国呼吸细胞与分子生物学杂志》。

J Nakano, K Ohta et al.: "Antisense DNA of platelet derived growth factor (PDGF) suppresses murine pulmonary fibrosis with silica particles."Am J Respir Critical Care Med. 159. 71 (1999)

J Nakano、K Ohta 等人：“血小板衍生生长因子 (PDGF) 的反义 DNA 通过二氧化硅颗粒抑制小鼠肺纤维化。”Am J Respir Critical Care Med。

J Nakano, K Ohta, et al.: "Antisense DNA of platelet derived growth factor (PDGF) suppresses murine pulmonary fibrosis with silica particles"Am J Respir Critical Care Med. 159. 71 (1999)

J Nakano、K Ohta 等人：“血小板衍生生长因子 (PDGF) 的反义 DNA 通过二氧化硅颗粒抑制小鼠肺纤维化”Am J Respir Critical Care Med。