CCK-8调节脂多糖诱导ECV-304NF-κB表达的受体机制研究

发布时间：2018-10-15 18:18

【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
[Abstract]:Objective: lipopolysaccharide (lipopolysaccharide,LPS)-induced endotoxin shock is a common critical pathological process with a mortality of 50%. Vascular dysfunction, decreased circulatory resistance and progressive decrease of systemic blood pressure are the characteristic pathological changes of endotoxin shock. Vascular endothelial cell (vascular endothelial cell,VEC) is not only an important biological barrier of blood vessels, but also has endocrine function. Under physiological conditions, VEC endothelial nitric oxide synthase (eNOS) produces a moderate amount of nitric oxide (NO) involved in the regulation of vascular tension and the distribution of organ blood flow, and the expression of VEC inducible nitric oxide synthase (iNOS) is up-regulated during the pathogenesis of endotoxic shock. Increased activity and production of a large number of NO, lead to activation and dysfunction of VEC, while dysfunction of VEC occurs in vascular dysfunction. The regulation of iNOS expression is mainly at the gene level, and the nuclear factor 魏 B (nuclear factor- 魏 B NF- 魏 B plays an important role in the process of iNOS induced by LPS. NF- 魏 B can bind to iNOS gene promoter and regulate the transcription and expression of iNOS after NF- 魏 B activation. Therefore, the moderate inhibition of the activity of VEC NF- 魏 B can alleviate the VEC damage induced by NO induced by iNOS and improve the vascular dysfunction in endotoxic shock. Cholecystokinin octapeptide (cholecystokinin octapeptide,CCK-8) has a definite anti-shock effect. The results showed that CCK-8 could increase the mean arterial pressure (MAP) of rats with endotoxic shock and hemorrhagic shock, and CCK-8 could significantly reduce the VEC induced by LPS in vitro.
【学位授予单位】：河北医科大学
【学位级别】：硕士
【学位授予年份】：2006
【分类号】：R363

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