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Research to Elucidate the Underlying Mechanisms of Airway Hyperreactivity.

阐明气道高反应性潜在机制的研究。

基本信息

批准号：
60440045
负责人：
TAKISHIMA Tamotsu
金额：
$ 11.46万
依托单位：
TOHOKU UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (A)
财政年份：
1985
资助国家：
日本
起止时间：
1985 至 1988
项目状态：
已结题

项目摘要

To elucidate the underlying mechanisms of bronchial hyperreactivity we have employed several sorts of animal models originally developed by us as well as normal subjects and patients with asthma and COPD. A summary of the results and conclusions which the research has attained to the present is as follows;1) ype C influenza virus infection induced airway hyperresponsiveness in Beagle dogs, especially 1 to 3 weeks after the infection, when an increase in the number of ast cells and concentrations of histamine, TXB2 and PGF2alpha in BALF were observed. Histological study also revealed damage and desquamation of the epithelial cells of the airways, which may suggest dysfunction of the EDRF.2) Ascaris suum antigen inhalation produced a higher incidence rate of LAR (late asthmatic response) in sensitized guinea pigs with silica as an adjuvant. At the LAR a distinct eosinophilic infiltration was observed in the mucosal tissue. The LAR can be blocked by administration of the selective and com … More petitive leukotriene blocker, ONO-1078. Airway hyperresponsiveness was also observed after the LAR, and was sustained for three to four day, which is possibly attributable to eosinophil infiltration.3) Superoxide inhalation produced airway contraction and subsequent airway hyperresponsiveness in cats, which was blocked by the administration of SOD, a scavenger of superoxide. In another study SOD also attenuated the increase in airway responsiveness after ozone inhalation. The results indicate that superoxide is an important factor in the production of hyperresponsiveness in the airway.4) After blocking sympathetic and parasympathetic nerves, inhalation of capsaicin or citric acid produced a dilatation of constricted airways in cats and human subjects, which was blocked by hexamethonium (C6), a ganglion blocker, The results indicate bronchial C-fiber receptors as well irritant receptors are also the receptors for the NAIS, which composes the reflex pathways. In addition, the stimulation of the NAIS also inhibited the immediate allergic reaction, revealing a protection against increase in lung resistance as well as histamine concentration.5) Through the study of single submucosal glands taken from cat trachea the effects of the autonomic nerves, substance-P, and VIP on contraction and secretion were determined. We also found that a substance is produced by epithelial cells which inhibits the mucous secretion. Less

为了阐明支气管高反应性的潜在机制，我们采用了几种最初由我们开发的动物模型，以及正常受试者和哮喘和COPD患者。现将研究所得的结果和结论总结如下：1) C型流感病毒感染引起Beagle犬气道高反应性，特别是感染后1 ~ 3周，BALF中ast细胞数量和组胺、TXB2、pgf2 α浓度升高。组织学研究还发现气道上皮细胞的损伤和脱屑，这可能提示edrf功能障碍。2)在以二氧化硅作为佐剂的致敏豚鼠中，吸入蛔虫抗原可产生更高的LAR（晚期哮喘反应）发生率。在LAR处，粘膜组织可见明显的嗜酸性粒细胞浸润。通过使用选择性和竞争性更强的白三烯阻滞剂ONO-1078，可以阻断LAR。术后气道高反应性持续3 ~ 4天，可能与嗜酸性粒细胞浸润有关。3)猫吸入超氧化物可引起气道收缩和随后的气道高反应性，而超氧化物清除剂SOD可阻断这一反应。在另一项研究中，SOD也减弱了臭氧吸入后气道反应性的增加。结果表明，超氧化物是气道产生高反应性的重要因素。4)在阻断交感神经和副交感神经后，吸入辣椒素或柠檬酸可使猫和人的狭窄气道扩张，并被神经节阻滞剂六甲索铵（C6）阻断。结果表明，支气管c纤维受体和刺激受体也是NAIS的受体，它们构成了反射通路。此外，NAIS的刺激也抑制了即时过敏反应，显示出对肺阻力和组胺浓度增加的保护作用。5)通过对猫气管粘膜下单个腺体的研究，确定了自主神经、p物质和VIP对收缩和分泌的影响。我们还发现上皮细胞产生一种物质，抑制粘液分泌。少