Physiological role of NO in the airway epithelia

NO 在气道上皮细胞中的生理作用

• 批准号: 10670057
• 负责人: IWAMOTO Jun
• 金额: $ 2.11万
• 依托单位: ASAHIKAWA MEDICAL COLLEGE
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10670057/
• 关键词: Nitric Oxide; Airway; Epithelium; Oxygen consumption; 二酸化炭素産出量; 鼻腔; 繊毛運動

The upper airway epithelium largely consist of ciliated columnar cells. These cells are famous for the clearance function in the airway. The beating of cilia conveys and clears foreign bodies up to the pharynx. Inside the ciliated columnar cell, there are densely populated mitochondria which keep providing ATP to support the strenuous movement of the cilia. In order to investigate the function of the epithelium of the upper airway, we attempted to measure the 02 consumption and C02 production of epithelia with using a ventilatory gas sampling technique of nasal cavity. The nostrils were ventilated from one side to the other by an air-pump while the soft palate was voiuntarily closed by the subject. The sample gases were continuously monitored with a mass spectormeter and a NO analyzer for a real-time analysis of VO2, VCO2 and VNO on the MacLab system. VO2 was 1.2() SY. +-. []0.15 and VCO2 was 1.65 () SY. +-. [] 0.10 ml/min (mean () SY. +-. [] SD). R was 1.38 () SY. +-. [] 0.12. VNO was 537 () SY. +-. [] 1 13 (ml/min/nose). Anoxia evoked simultaneous reduction of VO2, VCO2 and VNO. This suggests that the partial pressure of oxygen in the airway is the major deteminant for the metabolism of the lining epithelium. The physiological significance of lower airway NO was aiso investigated in the isolated rabbit lung and the effect of anoxia (hypoxia) was found to be similar. VNO of exhaled NO varies with the level of airway O2 in the manner of Michaelis-Menten kinetics. We also found the linearity between PO2 and changes of pumonary artery pressure. These findings strongly suggest that epithelial NO is sensing the oxygen level in the airway and play a pivotal role in matching ventilation and perfusion.

上呼吸道上皮主要由纤毛柱状细胞组成。这些细胞在气道中以清除功能而闻名。纤毛的跳动将异物输送并清除到咽部。在纤毛柱状细胞内，有密集的线粒体，不断提供ATP，以支持纤毛的剧烈运动。为了研究上呼吸道上皮的功能，我们尝试使用鼻腔的呼吸气体采样技术来测量上皮的O2消耗和CO2产生。鼻孔通过空气泵从一侧通气到另一侧，同时受试者自愿关闭软腭。采用质谱仪和NO分析仪对样品气体进行连续监测，并在MacLab系统上对VO 2、VCO 2和VNO进行实时分析。VO 2为1.2SY。+-. []0.15，VCO 2为1.65（）SY。+-. [] 0.10 ml/min（平均值（）SY. +-. [] SD）。R为1.38 SY。+-. [] 0.12。VNO为537 SY。+-. [] 113（ml/min/鼻）。缺氧引起VO_2、VCO_2和VNO同时降低。提示气道氧分压是决定气道上皮代谢的主要因素。在离体兔肺中观察了下气道NO的生理意义，发现缺氧（低氧）对下气道NO的影响相似。呼出气NO的VNO随气道O2水平的变化符合Michaelis-Menten动力学。PO_2与肺动脉压变化呈线性关系。这些发现有力地表明，上皮NO在气道中感知氧水平，并在通气和灌注的匹配中发挥关键作用。

项目成果

服部正明 他: "鼻腔拡張テープが鼻腔横断面積と鼻腔抵抗に及ぼす影響について"臨床スポーツ医学. 15. 1041-1045 (1998)

Masaaki Hattori 等人：“鼻腔扩张带对鼻腔横截面积和鼻腔阻力的影响”临床运动医学 15. 1041-1045 (1998)。

河野透他: "LPS微量前投与による実験的急性肝障害防御作用の検討"薬理と治療. 27. s1491-1493 (1999)

Toru Kono 等人：“小剂量 LPS 预给药对实验性急性肝损伤的保护作用的检查”药理学和治疗 27. s1491-1493 (1999)。

河野透他: "エンドトキシン血症時におけるNOと抗炎性サイトカインの関連に関する研究"薬理と治療. 27. s835-838 (1999)

Toru Kono 等人：“内毒素血症期间 NO 和抗炎细胞因子之间关系的研究”药理学和治疗 27. s835-838 (1999)。

Kakuya F,et al.: "Inhaled nitric oxide therapy via nasopharyngeal tube in an infant with end-stage pulomonary hypertension"Acta Paediat.Jap. 40. 155-158 (1998)

Kakuya F 等人：“通过鼻咽管吸入一氧化氮治疗患有终末期肺动脉高压的婴儿”Acta Paediat.Jap。

河野透、岩元純他: "エンドトキシン研究2"菜根出版(紀伊国屋書店). (1999)

河野彻、岩本淳等人：《内毒素研究 2》Nane Publishing（纪伊国屋书店）（1999 年）。