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Involvements of NO and histamine in radiographic contrast medium-induced pulmonary dysfunction

NO 和组胺参与放射造影剂诱发的肺功能障碍

基本信息

批准号：
13672390
负责人：
OISHI Ryozo
金额：
$ 2.24万
依托单位：
Kyushu University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2002
项目状态：
已结题

项目摘要

Although radiographic contrast media (RCM) are increasingly used for radiography and magnetic resonance imaging, undesirable actions associated with intravascular injection of RCM such as anaphylactoid adverse reactions and pulmonary dysfunction occur occasionally and no prevention or effective therapy for the adverse events has not been established. The present study was performed to determine the possible mechanisms underlying the RCM-induced pulmonary dysfunction and to propose a useful agent for the cure or prevention of servere adverse reaction to RCM. The research results as follows:1. RCM causes the degranulation of pulmonary mast cells and resultant release of histamine (HA) that in turn increases vascular permeability by stimulating H_1 and H_2 receptors.2. A variety of RCM stimulated HA release from rat pulmonary cells, in which the action of ionic RCM was more pronounced than that of non-ionic materials. It was clarified that the decrease in cellular cyclic AMP content and an increase in intracellular Ca^<2+> contributed largely to mast cell HA release induced by ionic RCM.3. Ioxaglate, an ionic RCM, induces pulmonary dysfunction by stimulating the release of mast cell tryptase. A clinically available nafamostat mesilate is potentially useful for the prevention or cure of anaphylactoid adverse reactions to the intravascular RCM injection.4. Mast cell tryptase impairs endothelial barrier function through activation of endothelial proteinase-activated receptor-2 in a manner dependent on the phospholipase C activity.5. Carbazochrome is a potentially useful for the prophylaxis of RCM-induced acute pulmonary adverse events. The stablization of endothelial barrier function may be associated with such a protective action of carbazochrome.

尽管放射造影剂（RCM）越来越多地用于放射摄影和磁共振成像，但与血管内注射RCM相关的不良反应（如过敏样不良反应和肺功能障碍）偶尔发生，并且尚未确定对不良事件的预防或有效治疗。本研究旨在探讨RCM引起肺功能不全的可能机制，并提出一种治疗或预防RCM严重不良反应的有效药物。研究结果如下：1. RCM引起肺肥大细胞脱颗粒，释放组胺（HA），通过刺激H_1和H_2受体增加血管通透性.各种RCM刺激大鼠肺细胞释放HA，其中离子型RCM的作用比非离子型材料更明显。结果表明，细胞内cAMP含量的降低和细胞内Ca^<2+>的增加在很大程度上促进了离子型RCM诱导的肥大细胞HA释放。碘克酸盐是一种离子型RCM，通过刺激肥大细胞类胰蛋白酶的释放诱导肺功能障碍。临床上可获得的甲磺酸萘莫司他可能用于预防或治疗血管内RCM注射剂的过敏样不良反应。肥大细胞类胰蛋白酶通过依赖于磷脂酶C活性的方式激活内皮蛋白酶激活受体2而损害内皮屏障功能.卡络磺是一种潜在的有用的预防RCM引起的急性肺部不良事件。稳定内皮屏障功能可能与卡络磺的这种保护作用有关。