Effects of Hypoxic on Bronchoplumonary Neuroepithelial Bodies (Paraneurons)

支气管肺神经上皮小体（bronchopulpulmonary neuroepithelial bodies, neb）是由含有胺和肽的细胞簇组成的，广泛分布于人和动物肺的气道粘膜。在结构上，neb类似于化学感受器，如颈动脉体、味蕾，被认为是缺氧敏感的气道传感器。利用组织化学和组织免疫化学技术，neb已被证明在其细胞质囊泡中含有5-羟色胺（5-HT）和肽样物质。在肺泡缺氧情况下，neb已被证明可将囊泡释放到细胞间隙。尽管这些细胞的氧感知机制及其释放的生理作用尚不清楚，但我们假设含有5-HT的囊泡的释放在肺血管收缩对吸入性缺氧的反应中起重要作用（hypoxic pulmonary vasocontraction， HPV）。本研究采用离体大鼠肺灌注模型，研究5-HT拮抗剂、酮色林、吸入麻醉剂、七氟醚、异氟醚对neb对缺氧和HPV反应的影响。对灌注物给予酮色林完全抑制肺血管收缩对吸入性缺氧的反应。从灌注液中洗去酮色林后，对HPV的抑制未恢复。这些发现有力地表明，导致HPV的介质是5-羟色胺，酮色胺与受体不可逆地结合。吸入麻醉剂七氟醚和异氟醚对HPV的抑制作用均呈剂量依赖性。吸入浓度为4%的七氟醚和3%的异氟醚完全阻断了这种反应。但肺血管对缺氧的反应在停止吸入60 min后恢复。麻醉剂对HPV的抑制作用是可逆的。

Bronchopulmonary neuroepithelial bodies (NEBs), composed of inervated clusters of amine-and peptide-containg cells, are widely distributed thoughout the airway mucosa of human and animal lungs. Structurally, NEBs resemble chemoreceptors such as corotid bodies, taste buds and are thought to function as hypoxia sensitive airway sensors. Using histchemical and histimmunochemical techniques, NEBs have been shown to contain serotonine (5-HT) and peptidelike substances in their cytoplasmic vesicles. Undre alveolar hypoxia, NEBs have been shown to release the vesicles to intercellular space. Though the mechanism of oxygen sensing by these cells and the physiological roles of the release are unknown, we hypothesize that the release of vesicles which contain 5-HT play essential roles in the responses of pulmonary vascular constriction to inhalational hypoxia (hypoxic pulmonary vasoconstriction(HPV). In this study, we used isolated lung perfusion models of rats and investigated the effects of 5-HT antagonist, ketanserin, and inhalational anesthetics, sevoflurane, isoflurane on the responses of NEBs to hypoxia and HPV.Administration of ketanserin to the perfusate completely inhibited the response of pulmonary vascluar constriction to inhalational hypoxis. The inhibition of HPV was not recovered after washout of ketanserin from the perfusate. These findings strongly suggest that the mediator which causes HPV is 5-HT and that ketanserin binds to the receptor irreversibly.Both inhalational anesthetics sevoflurane and isoflurane inhibited HPV dose dependedly. Inhalational concentrations of 4% sevoflurane and 3% isoflurane completely blocked the response. But the responses of pulmonary vessels to hypoxia was recovered at 60 min after cessation of inhalation. The inhibitory effects of the anesthetics on HPV were reversible.