血管活性肠肽对内毒素肺损伤启动的切断机制研究

项目名称： 血管活性肠肽对内毒素肺损伤启动的切断机制研究

项目编号： No.30870915

项目类型： 面上项目

立项/批准年度： 2009

项目学科： 医药、卫生

项目作者： 管茶香

作者单位： 中南大学

项目金额： 32万元

中文摘要： 急性肺损伤(ALI)是临床常见的危重症，其发生发展过程可分为早期的急性炎性损伤、中期的肺细胞激活和成纤维细胞增殖以及后期的肺组织胶原沉积三个阶段。血管活性肠肽（VIP）是肺内重要的神经肽，我们在证实VIP具有显著的促气道上皮细胞损伤修复作用的基础上进一步观察VIP在ALI中整体效应。因VIP在血浆中半衰期很短,本课题通过构建VIP过表达慢病毒，观察VIP对ALI的保护作用。小动物呼吸检测系统BUXCO检测表明VIP可增加ALI小鼠的呼吸频率、肺顺应性和潮气量，并降低其气道阻力。VIP可减少肺内白细胞的募集及蛋白渗出，降低肺组织乳酸脱氢酶活性和丙二醛的含量，增强超氧化物歧化酶的活性；抑制核转录因子NF-κ#30340;活化，降低肺组织中炎症启动因子TNF-α34920;达而增加IL-10的表达。进一步实验观察到，VIP可通过调节CREB磷酸化发挥促损伤修复的效应,并表现出一定的抑制肺纤维化的作用。首次报道VIP下调ALI时肺内炎症因子的表达，减轻肺内脂质氧化程度，促气道上皮损伤修复，提示VIP对内毒素ALI的早期自动瀑布式反应呈现出较好的切断效应，参与调整神经肽-炎症反应网络回复到生理状态的过程。

中文关键词： 血管活性肠肽；肺损伤；启动；切断机制

英文摘要： Acute lung injury (ALI) is common and devastating complication in clinic. The progress of ALI can be divided into three phases: (I) exudative phase characterized by cytokine production and increased inflammation (II) proliferative phase and (III) fibrotic phase. Vasoactive intestinal peptide (VIP) is an important neuropeptide in lungs. We reported that VIP could significantly promote the wound healing of airway epithelium. However, the short half-life of VIP in plasma results in the limitation of further observation of the overall effect of VIP on ALI. VIP lentviral was building. Small animal respiration test system (BUXCO research systems) showed that VIP could increase the respiratory rate, lung compliance and tidal volume, and lower breathing resistance in ALI mouse. VIP can reduce the infiltration of white blood cell and protein, lower the activity of lactate dehydrogenase and malondialdehyde content, and enhance the activity of superoxide dismutase in lung. VIP also could down-regulate the expression of TNF-alpha but increase IL-10 expression by inhibiting the activation of nuclear transcription factor (NF-κ. We also reported that VIP promoted the wound healing by regulating the transcription factor CREB phosphorylation, and inhibited pulmonary fibrosis. We first reported VIP could down-regulate inflammatory expression, alleviate the lipid oxidation, promote airway epithelial wound healing, and present a powerful effect on cutting off the automatically waterfall response in LPS-induced ALI, contributing to the homeostasis of neuropeptides inflammation network.

英文关键词： vasoactive intestinal peptide; lung injury; start; cut off mechanism