Study of the mechanism of lung vascular permeability in pulmonary edema

已知多种化学介质与渗透性肺水肿的发生有关。我们通过大池注射纤维蛋白原和凝血酶的大鼠模型（神经源性肺水肿模型）研究了神经源性肺水肿的机制，发现交感神经末梢同时释放神经肽Y （NPY）和神经激肽a，增加肺血管通透性。在NPY方面，我们报道了一项开创性的工作，通过孤立的灌注肺模型和刺激交感神经证明NPY是通透性物质之一。我们还阐明，在同一模型中，气管内给予NPY可以剂量抑郁性地增加肺血管通透性。在接下来的研究中，我们通过免疫组化方法发现NPY在水肿液和肺泡巨噬细胞中均存在，其浓度比在血浆中高1000倍。在本研究中，我们仔细研究了一氧化氮（NO）对肺水肿发展的影响。本研究结果提示，神经源性肺水肿的机制与交感神经末梢释放NPY等化学介质外周相关，与中枢神经系统NO相关。此外，在对迷走神经几天前被切断的大鼠进行的初步研究中，完全避免了神经性肺水肿。虽然其确切机制尚不清楚，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。

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.