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Study of the mechanism of lung vascular permeability in pulmonary edema

肺血管通透性在肺水肿中的作用机制研究

基本信息

批准号：
09470325
负责人：
SHIMADA Yasuhiro
金额：
$ 9.34万
依托单位：
NAGOYA UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1999
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09470325/
关键词：
neurogenic pulmonary edema lung vascular permeability central nervous system pulmonary edema neuropeptide Y sympathetic nervous system nitric oxide 血管透過性亢進神経伝達物質 ARDS neropeptide Y neuropepetides 肺循環

项目摘要

A variety of chemical mediators has been known to be responsible for the development of permeability pulmonary edema. We have been investigating the mechanisms of neurogenic pulmonary edema by using a rat model in which fibrinogen and thrombin are injected into the cisterna magna (neurogenic pulmonary edema model), and have found that neuropeptide Y (NPY) and neurokinin A, simultaneously released from the sympathetic nerve terminal, increase pulmonary vascular permeability. In terms of NPY, we reported a pioneer work in which NPY is proved to be one of the permeability substances by using an isolated perfused lung model and stimulating the sympathetic nerve. We also clarified that NPY administered intratracheally increases lung vascular permeability dose-despondently in the same model. In the following study, we have found that NPY is present both in the edema fluid and in alveolar macrophages and the concentration is 1000 times higher than that found in plasma by using an immunohistochemical method.In the present study, we have meticulously studied the effect of nitric oxide (NO) on the development of pulmonary edema. The present results may suggest that the mechanism of neurogenic pulmonary edema is peripherally related to the release of chemical mediators such as NPY from the sympathetic nerve terminal, and centrally related to NO in the central nervous system. Also in a preliminary study of rats in which the vagus nerve was severed several days before, neurogenic pulmonary edema was completely avoided. Although the precise mechanism is still not clear, the development of neurogenic pulmonary edema may be closely related to the effects of NO in the central nervous system and NPY in the peripheral sympathetic nerve terminal.

各种化学介质已被认为是负责的渗透性肺水肿的发展。我们一直在研究神经源性肺水肿的机制，通过使用大鼠模型，其中纤维蛋白原和凝血酶被注射到小脑延髓池（神经源性肺水肿模型），并发现神经肽Y（NPY）和神经激肽A，同时从交感神经末梢释放，增加肺血管通透性。在神经肽Y方面，我们报道了一个开创性的工作，其中通过使用离体灌流肺模型和刺激交感神经证实了神经肽Y是渗透性物质之一。我们还阐明，在同一模型中，血管内给予NPY可剂量依赖性地增加肺血管通透性。本研究采用免疫组织化学方法，发现肺水肿液和肺泡巨噬细胞中均存在NPY，其浓度比血浆中高1000倍，并详细研究了一氧化氮（NO）在肺水肿发生发展中的作用。提示神经源性肺水肿的发病机制可能与交感神经末梢释放NPY等化学介质有关，而与中枢NO有关。此外，在对大鼠的初步研究中，迷走神经在几天前被切断，神经源性肺水肿完全避免。虽然确切的机制尚不清楚，但神经源性肺水肿的发生可能与中枢神经系统NO和外周交感神经末梢NPY的作用密切相关。