CCK-8对LPS诱导ECV-304 iNOS表达的调节作用及其信号转导机制的研究
发布时间：2018-11-11 11:19
【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
[Abstract]:Endotoxin shock is one of the most common shock types in clinic, and the death rate is very high. The main cause of endotoxic shock is severe exogenous infection and poisoning. In the practice of forensic medicine, severe trauma, loss of blood and severe stress can cause the decrease of blood pressure of systemic circulation or the redistribution of blood in the body, resulting in intestinal mucosal ischemia and disturbance of local immune function, and the destruction of intestinal mucosal barrier function. Intestinal endotoxin lipopolysaccharide (lipopolysaccharide,LPS) is a common cause of endotoxemia. The disturbance of vascular regulation mechanism is one of the characteristic pathological changes of endotoxic shock. The main manifestations are the decrease of aortic pressure in early stage of endotoxic shock, the increase of pulmonary artery pressure and the abnormal changes of vascular reaction in isolated pulmonary artery and aorta. It has been found that vascular endothelial cells (vascular endothelial cells, VEC) can synthesize many vasoactive substances, which is the key factor to maintain the normal tension state and vascular reactivity of vascular. Nitric oxide (nitric oxide,NO) released by VEC is the first gas messenger molecule which has obvious vascular activity and mediates endothelium-dependent vasodilation. During endotoxic shock, VEC is the main target cell of LPS and many proinflammatory cytokines such as TNF,IL-1, and VEC inducible nitric oxide synthase (inducible nitric oxide synthase, iNOS) is activated. The activity of endothelial nitric oxide synthase (endothelial nitric oxide synthase, eNOS) is inhibited and the production of NO is impaired by NO, which is an important part of vascular reactivity and vascular regulation disorder. The proper regulation of VEC NO production is helpful to alleviate the disorder of vascular regulation mechanism in endotoxic shock and to alleviate the abnormal changes of hemodynamics, which is an important way to prevent and treat endotoxic shock. Cholecystokinin octapeptide (cholecystokinin octapeptide, CCK-8) is a very important neuroregulatory peptide and has a definite anti-endotoxic effect. Pretreatment with CCK-8 in endotoxic shock rats could increase the mean arterial pressure and increase the pulmonary artery pressure, and increase the endothelium-dependent relaxation response of isolated pulmonary artery and thoracic aorta. The reduction of aortic reactivity to vasoconstrictor indicated that the antiendotoxic shock effect of CCK-8 has a peripheral vascular mechanism, which is related to the regulation of VEC NO production. However, the molecular mechanism of CCK-8 antishock, especially the molecular mechanism of regulating VEC NO production, has not been fully clarified, which needs further study. This subject
【学位授予单位】：河北医科大学
【学位级别】：博士
【学位授予年份】：2006
【分类号】：D919
[Abstract]:Endotoxin shock is one of the most common shock types in clinic, and the death rate is very high. The main cause of endotoxic shock is severe exogenous infection and poisoning. In the practice of forensic medicine, severe trauma, loss of blood and severe stress can cause the decrease of blood pressure of systemic circulation or the redistribution of blood in the body, resulting in intestinal mucosal ischemia and disturbance of local immune function, and the destruction of intestinal mucosal barrier function. Intestinal endotoxin lipopolysaccharide (lipopolysaccharide,LPS) is a common cause of endotoxemia. The disturbance of vascular regulation mechanism is one of the characteristic pathological changes of endotoxic shock. The main manifestations are the decrease of aortic pressure in early stage of endotoxic shock, the increase of pulmonary artery pressure and the abnormal changes of vascular reaction in isolated pulmonary artery and aorta. It has been found that vascular endothelial cells (vascular endothelial cells, VEC) can synthesize many vasoactive substances, which is the key factor to maintain the normal tension state and vascular reactivity of vascular. Nitric oxide (nitric oxide,NO) released by VEC is the first gas messenger molecule which has obvious vascular activity and mediates endothelium-dependent vasodilation. During endotoxic shock, VEC is the main target cell of LPS and many proinflammatory cytokines such as TNF,IL-1, and VEC inducible nitric oxide synthase (inducible nitric oxide synthase, iNOS) is activated. The activity of endothelial nitric oxide synthase (endothelial nitric oxide synthase, eNOS) is inhibited and the production of NO is impaired by NO, which is an important part of vascular reactivity and vascular regulation disorder. The proper regulation of VEC NO production is helpful to alleviate the disorder of vascular regulation mechanism in endotoxic shock and to alleviate the abnormal changes of hemodynamics, which is an important way to prevent and treat endotoxic shock. Cholecystokinin octapeptide (cholecystokinin octapeptide, CCK-8) is a very important neuroregulatory peptide and has a definite anti-endotoxic effect. Pretreatment with CCK-8 in endotoxic shock rats could increase the mean arterial pressure and increase the pulmonary artery pressure, and increase the endothelium-dependent relaxation response of isolated pulmonary artery and thoracic aorta. The reduction of aortic reactivity to vasoconstrictor indicated that the antiendotoxic shock effect of CCK-8 has a peripheral vascular mechanism, which is related to the regulation of VEC NO production. However, the molecular mechanism of CCK-8 antishock, especially the molecular mechanism of regulating VEC NO production, has not been fully clarified, which needs further study. This subject
【学位授予单位】：河北医科大学
【学位级别】：博士
【学位授予年份】：2006
【分类号】：D919
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相关期刊论文 前10条
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