细胞因子在特发性肺间质纤维化血管生成中的作用

The potential role of cytokine expression and its relation to angiogenesis in idiopathic pulmonary fibrosis

目的 通过研究特发性肺间质纤维化（ＩＰＦ） 患者开胸肺活检标本中胰岛素样生长因子（ＩＧＦ）Ⅰ和血小板衍生生长因子（ＰＤＧＦ） 的表达，进一步阐明它们在ＩＰＦ过程中的作用。方法 采用免疫组化和原位杂交方法，分别利用ＩＧＦⅠ和ＰＤＧＦ的特异抗体和特异引物，检测其在ＩＰＦ患者开胸肺活检标本中的分布和表达。结果 在ＩＰＦ患者中，ＩＧＦⅠ主要分布在肺动脉血管、新生血管的平滑肌细胞和内皮细胞。肺泡巨噬细胞、Ⅱ型上皮细胞和间质细胞染色阳性。ＰＤＧＦ定位于增生的细支气管、Ⅱ型肺泡上皮细胞和间质成纤维细胞，肺泡巨噬细胞、血管内皮和平滑肌细胞也有较强着色。结论 ＩＧＦⅠ和ＰＤＧＦ可促进新生血管的产生及肺血管平滑肌细胞肥大、增生，在ＩＰＦ进程中起重要作用；同时，通过与肺实质细胞的相互作用，参与上皮细胞增生和修复、间质细胞增生和胶原沉积。

Objective The expression of insulin like growth factor(IGF) Ⅰ and platelet derived growth factor (PDGF) in open lung biopsies from patients with idiopathic pulmonary fibrosis (IPF) was studied to investigate their precise role in the development of fibrosis in IPF. Methods The distribution and expression of IGF Ⅰ and PDGF were examined in lung sections of IPF patients with antibodies and cDNA probes of IGF Ⅰ and PDGF by immunohistochemistry and in situ hybridization. Results IGF Ⅰ was predominantly localized in vascular smooth muscle cells and vascular endothelial cells of newly formed vessels in IPF. Smooth muscle cells of pulmonary arteries which underwent hypertrophy and hyperplasia strongly expressed IGF Ⅰ(+++). Type Ⅱ cells, alveolar macrophages, and interstitial cells were also stained with anti IGF Ⅰ, but with lesser intensity (+). PDGF AA and BB were localized in hyperplastic bronchio alveolar epithelial cells and interstitial fibroblasts (+++). Alveolar macrophages, vascular endothelial cells and smooth muscle cells were also stained positive (++). Conclusion IGF Ⅰ and PDGF promote angiogenesis and vascular smooth muscle cell hypertrophy and hyperplasia, which contribute to the progression of fibrosis in IPF. IGF Ⅰand PDGF are also involved in reepithelization and fibroproliferation in IPF through interaction with mesenchymal cells.