Basic study to establish artificial lung with metabolic functions

建立具有代谢功能的人工肺的基础研究

• 批准号: 03454234
• 负责人: KITAMURA Satoshi
• 金额: $ 3.97万
• 依托单位: Jichi Medical School
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1992
• 资助国家: 日本
• 起止时间: 1992 至 无数据
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-03454234/
• 关键词: Artifioal lnng; Arachidonic acid; Alveolar macrophage; Endothelial cell; Leukotriene; Prostaglandin; Thromboxane; Endotheline

Basic experiments were performed about alveolar macrophages and endothelial cells for these two years.Arachidonic acid metabolism of alveolar macrophages was analyzed by guinea pig alveolar macrophages. Macrophages were obtained by bronchoalveolar lavage, and incubated with arachidonic acid and A23187 for 5 minutes. Metabolites of supernatant were analyzed by reverse phase high-performance liquid chromatography. Leukotriene B_4, 5-HETE, and HHT were detected and the production of thromboxane A_2 was also speculated. Because these metabolites have very high chemotactic and bronchoconstrictive activities, it may be suggested that the metabiolites of arachidonic acid are very important to maintain the homeostasis of pulmonary function.On the other hand, metabolic functions of cultured endothelial cells were analyzed under the influence of leukotrienes, nicotine, and elastase. Leukotriene B_4 and D_4 stimulated the release of prostaglandin I_2 and thromboxane B_2 from endothelial cells. Nicotine inhibited the release of prostaglandin I_2, thromboxane B_2 and endotheline from endothelial cells in higher concentration. Elastase inhibited the permeability of cultured monolayer of endothelial cells. These results demonstrate that endothelial cells can regulate not only tonus of smooth muscle of airway and blood vessels but also chemotactic activities through the release of various chemical mediators.These basic data will provide us some basic information to establish an artificial lung with metabolic function.

这两年进行了肺泡巨噬细胞和内皮细胞的基础实验。用豚鼠肺泡巨噬细胞分析了花生四烯酸在肺泡巨噬细胞中的代谢。支气管肺泡灌洗获得巨噬细胞，花生四烯酸和A23187孵育5分钟。用反相高效液相色谱法分析上清液的代谢物。检测白三烯B_4、5-HETE和HHT，并推测血栓素A_2的生成。由于这些代谢物具有非常高的趋化和支气管收缩活性，因此可能提示花生四烯酸的代谢物对维持肺功能的稳态非常重要。另一方面，分析了培养的内皮细胞在白三烯、尼古丁和弹性酶的影响下的代谢功能。白三烯B_4和D_4刺激内皮细胞释放前列腺素I_2和血栓素B_2。高浓度尼古丁可抑制内皮细胞释放前列腺素I_2、血栓素B_2和内皮素。弹性蛋白酶抑制内皮细胞单层的通透性。这些结果表明，内皮细胞不仅可以调节气道和血管的平滑肌张力，还可以通过释放多种化学介质调节趋化活性。这些基础数据将为建立具有代谢功能的人工肺提供一些基础资料。