Fang Hsin-Yuan, Lin Ching-Yuang, Chow Kuan-Chih, Huang Hung-Che, Ko Wen-Je
Division of Thoracic surgery, Department of Surgery, China Medical University Hospital, China Medical University, Taichung, Taiwan.
Exp Lung Res. 2010 Aug;36(6):323-30. doi: 10.3109/01902141003628579.
Primary spontaneous pneumothorax (PSP) often occurs after the rupture of small bullae or subpleural blebs in otherwise normal lungs. The underlying mechanism(s) remain unclear. The aim of this study was to identify genes potentially involved in the development of PSP. Microarray analysis was performed to identify specific gene expression patterns. Expression levels of genes identified to be significantly up- or down-regulated in association with PSP were confirmed by real-time polymerase chain reaction (qRT-PCR) and Western blotting. Immunohistochemistry was performed to identify lung cell types highly expressing these genes. Microarray analysis revealed that expression levels of hypoxia-inducible factor-3 alpha (HIF-3alpha) and caspase-8 were significantly up-regulated in tissue from patients with PSP, whereas interferon-gamma, interleukin (IL)-6, and IL-8 were down-regulated (all P < .05). These genes are related to hypoxia, apoptosis, and inflammation. HIF-3alpha and caspase-8 protein levels were increased in samples from patients with PSP. HIF-3alpha and caspase-8 were localized in mesothelial cells, alveolar type II pneumocytes, and bronchoalveolar epithelial cells in samples from patients with PSP. Our findings, although obviously preliminary given the small sample size, suggest that hypoxia, inflammation, and apoptosis may play important roles in the pathogenesis of PSP.
原发性自发性气胸(PSP)常发生于原本正常的肺组织中小气泡或胸膜下肺大疱破裂之后。其潜在机制仍不清楚。本研究的目的是鉴定可能参与PSP发生发展的基因。进行微阵列分析以确定特定的基因表达模式。通过实时聚合酶链反应(qRT-PCR)和蛋白质印迹法证实了与PSP相关的显著上调或下调基因的表达水平。进行免疫组织化学以鉴定高表达这些基因的肺细胞类型。微阵列分析显示,缺氧诱导因子-3α(HIF-3α)和半胱天冬酶-8在PSP患者组织中的表达水平显著上调,而干扰素-γ、白细胞介素(IL)-6和IL-8则下调(均P <.05)。这些基因与缺氧、细胞凋亡和炎症相关。PSP患者样本中HIF-3α和半胱天冬酶-8的蛋白水平升高。HIF-3α和半胱天冬酶-8定位于PSP患者样本中的间皮细胞、II型肺泡上皮细胞和支气管肺泡上皮细胞中。尽管鉴于样本量小,我们的发现显然是初步的,但提示缺氧、炎症和细胞凋亡可能在PSP的发病机制中起重要作用。