Study on the Mechanism of Increased Vascular Permeability in Pulmonary Edema

我们研究了神经递质对肺血管通透性的作用机制，并就交感神经系统中与去甲肾上腺素共存的神经肽Y （NPY）在肺水肿发生中的作用得到如下结果。1)在离体灌注肺模型上研究交感神经刺激对肺血管通透性的影响。电刺激使肺重量增加，表明肺血管通透性增加。肺重量的增加发生在去甲肾上腺素阻滞剂的存在下，提示存在除去甲肾上腺素以外的血管活性物质。2)采用离体肺灌注模型，NPY和神经激肽A （NKA）均升高毛细血管通透系数（Kfc），降低降钙素基因相关蛋白（CGRP）。3)通过向肺模型的灌注液中注入碳颗粒，并在显微镜下计算肺泡中存在的碳颗粒，可以阐明肺血管的通透性。NPY注入气管后，肺泡内碳颗粒数量呈剂量依赖性显著增加。4) npyy_3受体的部分拮抗剂NPY_<18-36>预处理可延长纤维蛋白肺水肿模型的水肿形成时间，降低肺泡液与血清的蛋白浓度比。5) NPY_<18 ~ 36>预处理可减少气管内NPY处理动物肺泡内碳颗粒数量。

We investigated the role of neurotransmitters on the mechanism of pulmonary vascular permeability, and the following results were obtained in terms of the role of neuropeptide Y (NPY), which co-exists with norepinephrine in the sympathetic nervous system, on the development of pulmonary edema.1)We studied the effect of sympathetic nerve stimulation on lung vascular permeability on isolated perfused lung model. Electrical stimulation increased the lung weight, suggesting an increase in lung vascular permeability. The increase in lung weight occurred in the presence of norepinephrine blockers, suggesting the presence of vasoactive substances other than norepinephrine.2)By using the isolated perfused lung model, NPY and neurokinin A (NKA) showed an increase in capillary permeability coefficient (Kfc), and calcitonin-gene related protein (CGRP) showed a decrease.3)Lung vascular permeability can be elucidated by injecting carbon particlesinto the perfusate of the lung model and microscopically calculate the carbon particles present in the alveoli. Administration of NPY into the trachea caused a significant increase in the number of carbon particlesin the alveoli in a dose-dependent manner.4)Pretreatment with NPY_<18-36>, which is a partial antagonist of NPY Y_3 receptor, elongated the time required for edema formation and reduced the protein concentration ratio of alveolar fluid to serum in the fibrin pulmonary edema model.5)Pretreatment with NPY_<18-36> reduced the number of carbon particlesin the alveoli in the animals treated with NPY intratracheally.