【作者】 平静；

【导师】 谷振勇；

【作者基本信息】 河北医科大学 ， 法医学， 2006， 硕士

【摘要】 目的：脂多糖(lipopolysaccharide，LPS)引起的内毒素休克是一种常见的危重病理过程，死亡率可达50％～80％。血管功能紊乱、循环阻力降低及体循环血压进行性降低是内毒素休克的特征性病理变化之一。业已公认，血管内皮细胞(vascular endothelial cell，VEC)不仅是机体血管的重要生物屏障，而且还具有内分泌功能。在生理条件下，VEC的内皮型一氧化氮合酶(eNOS)产生适量一氧化氮(NO)参与调节血管紧张度和器官血流量的分布；在内毒素休克发病过程中，VEC的诱导型一氧化氮合酶(iNOS)表达明显上调、活性增高并产生大量的NO，导致VEC的激活和功能障碍，而VEC功能障碍在血管功能紊乱、循环衰竭的发生中至关重要。iNOS的表达调控主要在基因水平进行，VEC核因子κB(nuclear factor-κB，NF-κB)在LPS诱生iNOS过程中起重要作用，NF-κB激活后能与iNOS基因启动子结合，调节iNOS的转录和表达。因此，若能适度抑制VEC NF-κB的活性，有助于减轻由iNOS诱生NO所导致的VEC损伤，改善内毒素休克血管功能紊乱。 八肽胆囊收缩素(cholecystokinin octapeptide，CCK-8)具有明确的抗休克作用。研究表明，CCK-8可使内毒素休克和失血性休克大鼠的平均动脉压(MAP)回升，提高其生存率；在离体条件下CCK-8可明显减轻LPS诱导的VEC更多还原

【Abstract】 Objective: Endotoxic shock induced by gram-negative bacteria lipopolysaccharide is a very dangerous pathologic process with mortality of 50%~80% and is characteristic of the disorders of blood vessels with depressed resistence of systemic circulation and continuous fall in mean arterial pressure. It has been well known that vascular endothelial cells (VEC) are one of the major target of endotoxin, and VEC are not only a mechanical and biological barriers of blood vessles, but also an important endocrine organ, participating in the regulation of vascular tone and blood flow distribution of organs via release of vasoactive substances such as nitric oxide (NO). Under the physiological circumstance, VEC produces the appropriated quantities of NO from the endothelial-type NO synthase (eNOS), playing as physiological regulation functions, whereas during the endotoxic shock, the upregulation of inducible NO synthase (iNOS) expression in VEC can be induced with enhanced activity of iNOS and the generation of large quantities of NO led to over-activation and dysfunctions of VEC, and resulted in the disorders of vascular regulations and circulation failure. The control of iNOS expression is at gene. The activation of NF- κB更多还原