项目名称: 低脂联素血症在高脂诱发动脉血栓形成中的作用及机制
项目编号: No.81470413
项目类型: 面上项目
立项/批准年度: 2015
项目学科: 医药、卫生
项目作者: 李榕
作者单位: 中国人民解放军第四军医大学
项目金额: 73万元
中文摘要: 病理性血栓形成是多种心脑血管疾病的共同成因,而高脂血症是引发血栓性疾病的重要危险因素,但分子机理尚未完全阐明。我们前期研究表明,脂肪细胞因子脂联素具有改善内皮功能及抑制血小板活化作用,预实验研究进一步表明,氧化/硝化应激可能在其中发挥重要作用;我们新近的临床研究发现,高脂血症患者脂联素水平显著降低。据此我们提出科学假设:高脂血症时脂联素水平下降是导致内皮功能紊乱和血小板活化增强从而易形成血栓的重要环节,其机制与血管内皮及血小板氧化/硝化应激增强有关。本课题拟采用药理学与基因干预方法,揭示高脂血症血浆脂联素水平/活性与血小板活性的因果关系,阐明脂联素对血管内皮与血小板氧化/硝化应激的调节效应,并采用高脂血症血栓模型及脂联素敲除动物,验证低脂联素血症在高脂诱发血栓形成中的作用。阐明上述问题,可为深入认识脂联素心血管作用提供新的实验依据、并为防治高脂血症血栓性疾病提供新策略和新靶点。
中文关键词: 脂联素;高脂血症;血栓形成;血小板聚集;内皮功能
英文摘要: Thrombus formation contributes greatly to cardia-cerebrovascular diseases. Hyperlipidemia plays a key role in thrombotic diseases. However, the molecular mechanisms of hyperlipidemia-induced thrombosis remain elusive. Our previous study demonstrated that treatment with adiponectin improves endothelial function and inhibits platelets aggregation. Preliminary experiments further revealed that the endothelial and platelet regulatory effects of adiponectin may involve attenuating oxidative/nitrative stress. Our recent clinical research showed that plasma levels of adiponectin is significantly reduced in hyperlipidemic patients. The current grant application is designed to demonstrate the following novel hypothesis: Endothelial dysfunction and platelet aggregation caused by hypoadiponectinemia is a crucial factor in hyperlipidemia-induced thrombosis, which is largely attributable to augmented oxidative/nitrative stress. Utilizing pharmacology and gene interference methods, we aim to: 1)Clarify the relationship of the levels/activity of adiponectin with activity of platelet in hyperlipidemia; 2)Determine the regulative effects of adiponectin on oxidative/nitrative stress levels of endothelium and platelet; 3)Identify the effects of hypoadiponectinemia in hyperlipidemia-induced thrombosis by utilizing a hyperlipidemic thrombus model and adiponectin knockout animals. Verifying these problems will help us to understand whether and how the adipokine adiponectin influences the cardiovascular system and provide novel targets for preventing and treating the thrombopoiesis in hyperlipidemia.
英文关键词: adiponectin;hyperlipidemia;thrombus formation;platelet aggregation;endothelium function