【作者】 高峰；

【导师】 谷振勇； 丛斌；

【作者基本信息】 河北医科大学 ， 法医学， 2006， 博士

【摘要】 内毒素休克是临床常见的休克类型之一,死亡率极高,一直是医学研究的重点课题。内毒素休克的主要发生原因是严重的外源性感染、中毒;在法医学实践中,严重创伤、失血失液及严重应激可引起体循环血压下降或体内血液再分布,致使肠粘膜缺血及局部免疫功能紊乱、肠粘膜屏障功能破坏,肠源性内毒素脂多糖(lipopolysaccharide,LPS)入血,造成肠源性内毒素血症,也是内毒素休克发生的常见原因。血管调节机制紊乱是内毒素休克特征性病理改变之一,主要表现为内毒素休克发生早期主动脉压下降、肺动脉压升高以及离体肺动脉及主动脉血管反应异常变化。研究发现,血管内皮细胞(vascular endothelial cells, VEC)能合成多种血管活性物质,是维持血管正常张力状态和血管反应性的关键因素。其中VEC释放的一氧化氮(nitric oxide,NO)是人们发现的机体第一种气体信使分子,具有明显的血管活性、介导了血管内皮依赖性舒张反应。在内毒素休克过程中VEC是LPS及其诱导机体产生的多种促炎细胞因子如TNF、IL-1作用的主要靶细胞,VEC诱导型一氧化氮合酶(inducible nitric oxide synthase, iNOS)激活、NO大量诱生而内皮型一氧化氮合酶(endothelial nitric oxide synthase, eNOS)活性被抑制、NO生成障碍,是血管反应性异常变化、血管调节机制紊乱的重要发病环节。适当调控VEC NO生成有助于缓解内毒素休克血管调节机制紊乱、减轻血液动力学异常变化,成为防治内毒素休克的重要途径。八肽胆囊收缩素(cholecystokinin octapeptide, CCK-8)是一种十分重要的神经调节肽,具有明确的抗内毒素休克作用。用CCK-8预处理内毒素休克大鼠可使降低的平均动脉压回升而增高的肺动脉压降低,提高离体肺动脉、胸主动脉的血管内皮依赖性舒张反应,改善胸主动脉对缩血管剂反应性降低,表明CCK-8的抗内毒素休克效应存在着外周血管机制,与调控VEC NO生成有关。然而CCK-8抗休克作用的分子机制,特别是调控VEC NO生成的分子机制尚未完全阐明,有待于进一步探讨。本课题更多还原

【Abstract】 Endotoxin shock is a common and severe pathological process with high mortality, and has been one of the most important topics in biomedicine. In clinical practice bacterial infections are the most common cause for endotoxin shock. However, in forensic practice endotoxin shock can be caused by severe trauma and vigorous stress stimulation, which can lead to decrease in systemic blood pressure and redistribution of blood volume, subsequential intestinal membrane ischemia and local immunologic dysfuntions resulting in the disorders of intestinal membrane barriers and intestinal-originated endotoxin lipopolysaccharide (LPS) translocation into blood.The disorders of vascular regulations is characteristic of endotoxin shock with the manifestations of marked reduction in systemic mean arterial pressure whereas pulmonary arterial hypertension, as well as abnormal changes of vascular reactivities of systemic and pulmonary arteries at its initial stage. It has been well known that vascular endothelial cells (VEC) are not only a mechanical and biological barrier of blood vessels, but also an endocrine organ, which maintain vascular normal tension and reactivities througth synthesis and release vasoactive substances such as nitric oxide (NO). NO, a first gas information molecule discovered in human being, is a typical endothelial-derived relaxant and mediates endothelium-dependent relaxation of blood vessels. In the pathogesis of endotoxin shock VEC is one of the major target cells of LPS and LPS-induced proinflammatory cytokine such as tumor necrosis factor and interlukin 1 and activated. In VEC inducible nitric oxide synthase (iNOS) is induced and lead to an increase in production of NO, the while endothelial nitric oxide synthase (eNOS) is inhibited and elicit decrease in NO formation, both of which are demonstrated to induce the更多还原