气道上皮细胞的抗氧化损伤保护及微环境调控

Protection from Oxidant Injury on Airway Epithelial Cells and the Local Microenvironment Modulation

本工作建立了臭氧对原代培养的兔支气管上皮细胞（ＢＥＣ）损伤模型，观察到血管活性肠肽（ＶＩＰ）、表皮生长因子（ＥＧＦ）、热应激等微环境理化因子可减轻细胞损伤，具有细胞保护作用。其保护机制与提高还原型谷胱甘肽（ＧＳＨ）含量有关，并依赖于蛋白激酶的磷酸化调节及基因转录。ＢＥＣ细胞在基础情况下有ｂｃｌ２基因的低水平表达，ＶＩＰ和ＥＧＦ可促进ｂｃｌ２基因转录，增强ＢＥＣ的抗氧化损伤能力。ＥＧＦ或热应激促进ＢＥＣ自分泌ＶＩＰ，并上调ＢＥＣ表达ＶＩＰ受体（ＶＩＰＲ），可放大ＶＩＰ的局部保护效应。论证了气道上皮存在抗损伤自我保护机制，受到局部微环境中调节肽及外源性刺激的适应性调控。

Abstract An cellular injury model of primary cultured rabbit bronchial epithelial cells (BEC) exposed to ozone was established in this study and cytoprotective effects of factors in local microenvironment of airway such as vasoactive intestinal peptide (VIP), epidermal growth factor (EGF) and heat stress were observed. These factors could lighten damage in cell and elevate the level of glutashione(GSH), which depended upon phosphorylation modulation by protien kinases and gene transcription. A low level of bcl 2 gene expression could be detected in BEC at basic state, and either VIP or EGF stimulated the transcription of bcl 2, which improved the capability of BEC to resist oxidant injury. Otherwise, EGF and heat stress increased VIP autocrine from BEC and upregulated the expression of VIP receptor on BEC, so that the protective effect of VIP