CSE/H2S在内毒素急性肺损伤发生中的作用及其机制研究

项目名称： CSE/H2S在内毒素急性肺损伤发生中的作用及其机制研究

项目编号： No.30800440

项目类型： 青年科学基金项目

立项/批准年度： 2009

项目学科： 轻工业、手工业

项目作者： 黄新莉

作者单位： 河北医科大学

项目金额： 20万元

中文摘要： 背景和目的：新型气体信号分子硫化氢（H2S）在急性肺损伤（ALI）发生中具有重要作用。在此基础上本研究从中性粒细胞（PMN）和肺微血管内皮细胞（PMVEC）粘附，PMVEC、PMN凋亡及肺泡巨噬细胞对PMN清除等多方位，探讨CSE/H2S 在肺损伤发生中的确切作用及信号转导机制。主要内容：构建CSE cDNA 表达质粒和重组腺病毒载体，复制大鼠内毒素致ALI 模型，观察H2S对大鼠内毒素所致ALI、肺内PMN聚集及PMVEC和PMN 粘附、粘附分子表达及H2S作用的信号转导机制。主要结果：H2S可抑制PMN 在肺中聚集、发挥抗大鼠内毒素所致ALI 的作用；H2S具有抑制内毒素所致的PMN 和PMVEC粘附增强、下调粘附分子表达的作用；H2S具有抑制内毒素所致PMN 凋亡延迟的作用，并可增强肺泡巨噬细胞的吞噬能力的作用；H2S可显著抑制内毒素所致的PMVEC 凋亡；H2S发挥上述作用的信号转导机制与其对PI3-K→RK1/2→F-κ#36890;路的抑制有关。意义：阐明了CSE/H2S在内毒素急性肺损伤发生中的确切作用及机制，为临床防治内毒素急性肺损伤提供了新的理论基础和实验依据。

中文关键词： 内毒素；急性肺损伤；CSE；H2S；MAPK

英文摘要： Background and aim: Based on the previously studying result that hydrogen sulfide (H2S), a new gaseous signal molecule, could provide protection against acute lung injury(ALI) induced by endotoxin, the present study was designed to further study the role and molecular mechanisms of exogenous H2S in attenuating lung injury induced by endotoxin by gene transfection method. Main contents: The CSE cDNA expression plasmid and adenovirus vectors were established and the animal model of lung injury induced by endotoxin was made. The effects of exogenous H2S on the lung injury induced by endotoxin was observed. polymorphonuclear leukocyte (PMN) sequestration in the lung, the expressions of adhesion molecule in pulmonary microvascular endothelial cell (PMVEC)and PMN, the activities of PI3-K, mitogen-activated protein kinase (ERK1/2) and nucler factor-κNF-κ during ALI were detected. Main results: Exogenous H2S dose-dependently inhibited lung injury and PMN sequestration induced by endotoxin and significantly down regulated the expressions of adhesion molecule in PMN and PMVEC, and decreased their adhesion rate induced by endotoxin by a related mechanism of suppressing PI3-K→RK1/2→F-κsignal pathway; Exogenous H2S could accelerate PMN apoptosis and abrogate endotoxin-delayed apoptosis mediated by the suppression of PI3-K→RK1/2→F-κsignaling pathway; Exogenous H2S could suppress the endotoxin-induced PMVEC apopotosis and more specifically via the suppression activation of NF-κ Significance:The present work disclosed the protective role and its underlying mechanisms of exogenous H2S at a low dose in the lung injury induced by endotoxin, which lay a foundation for the prevention and treatment of acute lung injury induced by endotoxin.

英文关键词： endotoxin; acute lung injury; CSE; H2S; MAPK