Study of the mechanism of lung vascular permeability in pulmonary edema

已知多种化学介质导致通透性肺水肿的发生。我们采用大鼠枕大池注射纤维蛋白原和凝血酶的方法探讨神经源性肺水肿的发生机制，发现交感神经末梢同时释放神经肽Y(NPY)和神经激肽A可增加肺血管通透性。在NPY方面，我们报道了一项开创性的工作，通过使用隔离的肺灌流模型和刺激交感神经，证明NPY是一种通透性物质。我们还阐明了在相同的模型中，气管内给予NPY可剂量依赖性地增加肺血管通透性。在接下来的研究中，我们发现NPY同时存在于肺泡巨噬细胞和水肿液中，其浓度是免疫组织化学方法检测到的血浆浓度的1000倍。提示神经源性肺水肿的发生机制可能与交感神经末梢释放NPY等化学介质有关，与中枢神经系统的NO有关。在一项对几天前切断迷走神经的大鼠的初步研究中，神经源性肺水肿完全避免了。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的NO和周围交感神经末梢的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.