【作者】 郭志福；

【导师】 郑兴； 秦永文； 吴弘； 陈少萍； 胡建强；

【作者基本信息】 第二军医大学 ， 内科学， 2007， 博士

【摘要】 目的:探讨ghrelin和obestatin在冠心病及其危险因素肥胖症中的水平变化及其作用,并初步探讨其中机制。方法:采用放射免疫法检测肥胖症和冠心病患者外周血ghrelin、obestatin水平;观察obestatin对3T3-L1前脂肪细胞增殖和分化的影响;并采用Langendorff离体大鼠心脏灌流模型及缺血再灌注损伤模型,观察obestatin对正常离体心脏及缺血再灌注损伤的作用;以及obestatin对H5V血管内皮细胞增殖和细胞黏附分子表达的影响。结果:肥胖症患者餐前外周血obestatin相对水平明显降低。Obestatin可以明显抑制3T3-L1前脂肪细胞的增殖和分化。冠心病患者外周血obestatin的绝对和相对水平均明显升高。Obestatin可以通过Rho激酶及PI3-K途径加重离体心脏的缺血再灌注损伤。Obestatin可以明显抑制血管内皮细胞增殖,增加ICAM-1、VCAM-1表达,其中部分机制是通过Rho激酶及PI3-K途径。结论:冠心病和肥胖症患者外周血均存在ghrelin/obestatin水平失衡。Obestatin可能是一个新的冠心病危险因子。更多还原

【Abstract】 Objective: To investigate changes of circulating ghrelin and obestatin levels, their roles and mechanisms in coronary artery disease (CAD) and obesity.Methods: Plasma total ghrelin and obestatin levels were measured by RIA in CAD and obesity patients. Effect of obestatin on proliferation and differentiation of 3T3-L1 preadipocytes was investigated. Effects of obestatin on isolated rat hearts was investigated in normal and ischemia/reperfusion Langendorff models. Effect of obestatin on proliferation and expression of cell adhesion molecules of H5V endothelial cells was also investigated.Results: Circulating preprandial ghrelin to obestatin ratio was elevated in human obesity. Obestatin inhibited the proliferation and differentiation of 3T3-L1 preadipocytes. Both absolute and relative obestatin levels were increased in CAD patients. Obestatin could deteriorate cardiac function damage induced by ischemia and reperfusion in the Langendorf model of rat heart through the Rho kinase and PI3-K pathways. Obestatin inhibited the proliferation of endothelial cells through the Rho kinase and PI3-K pathways, and increased adhesion molecules expression.Conclusion: There is imbalance of circulating ghrelin and obestatin levels both in CAD and obesity patients, and obestatin may be a new risk factor of CAD.更多还原