中文摘要
我们临床研究发现冠心病合并脑血管粥样硬化狭窄大于50%的患者占61%,证实冠状动脉粥样硬化与脑血管粥样硬化存在密切关系。目前对于omega-3代谢产物抗动脉粥样硬化研究多仅涉及炎症方面,在心脑血管动脉粥样硬化程度方面研究较少。我们将运用经过冠状动脉造影及全脑血管造影的人血浆样本,通过代谢生物质谱技术和WB蛋白测定等,观察omega-3代谢产物RvE、RvD、PD1的含量活性与冠状动脉粥样硬化和脑血管粥样硬化病变的关系,利用细胞培养研究omega-3代谢产物和酶对于内皮细胞的迁移和增殖的影响及其机制,进一步研究在动脉粥样硬化状态下,omega-3代谢产物量的改变是否与COX2、LOX酶的含量和活性有关。从临床、细胞和动物模型探讨omega-3代谢与心脑血管动脉粥样硬化的关系,探讨RvE、RvD、PD1或者COX2、LOX有可能成为心、脑血管动脉粥样硬化程的新标志物
英文摘要
We analyzed the coronary angiography (CAG) and digital subtraction angiography (DSA) results of 97 symptomatic patients and found that 59 coronary atherosclerosis stenosis patients were combined with cerebral atherosclerosis stenosis greater than 50%(account for 61percentage), which declared the correlation of coronary and cerebral atherosclerosis. The inflammatory reaction theory had comprehensively explained the genesis and development of atherosclerosis among all the other theories in pathogenesis research. Now studies had proved that omega-3 metabolites had effects on anti-inflammation through many mechanisms, but few research of its effects on endothelial cells had been conducted. Studies had also proved the effects of omega-3 metabolites on the second prevention of coronary atherosclerosis, but the intake of omega-3 metabolites couldn't reduce the mortality for the atherosclerotic. We are now concentrating on the effects of the Omega-3 metabolites(RvE、RvD、PD1) on coronary and cerebral atherosclerosis.We are making further research of whether the quantitative change of omega-3 metabolites will influence the quantity and activity of the 2 synthetases closely related to its metabolism in the atherosclerosis. We will analyze the results of the patients' coronary and cerebral vessels with the coronary angiography (CAG) and digital subtraction angiography (DSA).Then we explore the relationship between the Omega-3 metabolites-RvE, RvD, PD1 ,the quantity and activity COX, LOX and the coronary and cerebral atherosclerosis. Simultaneously we will research the mechanism and the effects of Omega-3 metabolism on the migration and proliferation of endothelial cells and atherosclerotic rat models. We will discuss the relationship of omega-3 and atherosclerotic disease and find the new markers that reflects the relationship between coronary atherosclerosis and cerebral atherosclerosis.
结题摘要
Omega-3 和Omega-6脂肪酸属于必需多不饱和脂肪酸,在人体中不能合成,需要从食物中摄取。Omega-3脂肪酸对于心血管疾病的保护作用已经毋庸置疑,而Omega-6脂肪酸对心血管疾病的作用却各执一词。目前对于两者对心血管病的影响多停留在临床随机对照研究,对其代谢产物的研究还相对较少,尤其是Omega-6脂肪。Omega-3 和Omega-6脂肪酸代谢产物复杂,功能也不尽相同。本课题组通过收集正常组、 脑血管病组、 冠心病组、 冠心病合并脑血管病组的血浆样本,通过代谢生物质谱技术,观察omega-3代谢产物(78种代谢产物)和Omega-6(31种代谢产物)的含量与冠状动脉粥样硬化关系。结果发现AA_15-oxo-ETE在冠心病组血浆中明显增高,曾有研究在动脉粥样硬化的斑块中发现AA_15-oxo-ETE,但是目前对 15-oxo-ETE功能尚不清晰。我们通过细胞实验证明,AA_15-oxo-ETE会抑制内皮细胞修复,上调E-selectin的表达,促进单核细胞粘附。进一步的结果显示AA_15-oxo-ETE的这些影响很可能是通过PKC/NF-KB/E-selectin 这一通路进行调节的。对于AA_15-oxo-ETE的功能探索将为动脉粥样硬化的诊断预防及健康饮食指南提供更多的依据。
