过氧亚硝基阴离子介导内毒素致肺血管损伤及胆囊收缩素的保护作用

本文探讨过氧亚硝基阴离子（ONOO^-）在内毒素致肺血管损伤中的介导作用和八肽胆囊收缩素（CCK）的保护作用及其机制。结果发现，内毒素主要成分脂多糖（LPS）可诱导大鼠肺组织生成ONOO^-1,ONOO^-能导致肺微血管壁通透性明显增加和肺脏严重病理变化；ONOO^-可引起离体肺动脉反应性异常改变，LPS也可产生类似变化；ONOO^-有较弱的舒血管作用并受到内皮细胞的抑制性调节；LPS诱导培养的牛肺动脉内皮细胞（BPAEC）产生增多的ONOO^-参与介导内皮细胞本身的损伤；CCK能拮抗LPS对BPAEC的损伤效应，此作用由CCK受体介导，并与抑制ONOO^-生成有关。结果提示，清除ONOO^-或减少ONOO^-生成可为防治内毒素引起的急性肺损伤等病理过程提供新对策；CCK是一种有应用前景的细胞保护因子。

Peroxynitrite-mediated pulmonary vascular injury induced by endotoxin and the protective role of cholecystokinin

WT5BZ] This study was to investigate the mediation of peroxynitrite(ONOO -) in pulmonary vascular injury induced by lipopolysaccharide(LPS),a major component of bacterial endotoxin, and the protective effect of cholecystokinin octapeptide(CCK) and its underlying mechanism. The generation of ONOO - in rat lungs was induced by administration of LPS (5mg/kg iv). Exogenous ONOO - led to increase in microvascular permeability and severe pathologic changes of rat lungs. The exposure of isolated pulmonary artery segment to ONOO - resulted in abnormal reactivities similar to those induced by LPS. ONOO - caused weak relaxation which was negatively regulated by endothelial cells.The significantly increased production of endogenous ONOO - in cultured BPAEC elicited by LPS might mediate cytotoxic effects of LPS. The protection of CCK against the effects of LPS in isolated pulmonary artery or BPAEC was mediated by CCK receptors and related to the inhibition of ONOO - generation. These data indicated that scavenging ONOO - or decreased in ONOO - generation provided a novel therapeutic strategy for alleviation of LPS induced pathologic process such as acute lung injury,and that CCK may be an endogenous cytoprotective factor for promising practice.