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《Progress In Physiological Sciences》 2001-02
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Peroxynitrite-Mediated Pulmonary Vascular Injury Induced by Endotoxin and the Protective Role of Cholecystokinin

GU Zhen Yong (Department of Pathophysiology, Hebei Medical University, [WT5”BZ]Shijiazhuang 050017) [WT5HZ]  
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.
【Fund】: 国家自然科学基金!资助课题 (39870 317;;395 70 30 4)
【CateGory Index】: R363
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