Yerrapureddy Adi, Tobias John, Margulies Susan S
Department of Bioengineering University of Pennsylvania, Philadelphia, USA.
Cell Physiol Biochem. 2010;25(1):113-22. doi: 10.1159/000272056. Epub 2009 Dec 22.
Mechanical ventilation with large tidal volumes can increase lung alveolar permeability and initiate inflammatory responses; but the mechanisms that regulate ventilator-associated lung injury and inflammation remain unclear. Analysis of the genomic response of the lung has been performed in intact lungs ventilated at large tidal volumes. This study is the first to study the genomic response of cultured primary alveolar epithelial cells undergoing large and moderate physiologic cyclic stretch. Responses were dependent on stretch magnitude and duration. Genomic expression was validated for 5 genes of interest: Amphiregulin, Glutamate-Cysteine Ligase Catalytic subunit, Matrix Metalloproteinase 7, Protein Phosphatase 1 regulatory inhibitor subunit 10, and Serpine-1, and protein expression mirrored genomic responses. Differences between results reported from homogenized intact lungs and monolayers of alveolar epithelial cells with type-I like phenotype provide provocative evidence that the whole lung preparation may mask the response of individual cell types.
大潮气量机械通气可增加肺泡通透性并引发炎症反应；但调节呼吸机相关性肺损伤和炎症的机制仍不清楚。已在大潮气量通气的完整肺中进行了肺基因组反应分析。本研究首次研究了经历大、中度生理性周期性拉伸的原代培养肺泡上皮细胞的基因组反应。反应取决于拉伸幅度和持续时间。对5个感兴趣的基因进行了基因组表达验证：双调蛋白、谷氨酸-半胱氨酸连接酶催化亚基、基质金属蛋白酶7、蛋白磷酸酶1调节抑制剂亚基10和丝氨酸蛋白酶抑制剂-1，蛋白表达反映了基因组反应。来自匀浆完整肺和具有I型样表型的肺泡上皮细胞单层的结果差异提供了具有启发性的证据，表明全肺标本可能掩盖了单个细胞类型的反应。
