肝素酶过表达与脓毒症血管内皮功能不全的相关性研究

项目名称： 肝素酶过表达与脓毒症血管内皮功能不全的相关性研究

项目编号： No.81201449

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学四处

项目作者： 夏江燕

作者单位： 东南大学

项目金额： 23万元

中文摘要： 脓毒症时血管内皮损伤引发凝血级联激活、液体渗漏、循环机能障碍，继而发生脓毒性休克、多器官功能衰竭，在脓毒症发生、发展中起了重要的作用，目前血管内皮已成为脓毒症的治疗靶点，但脓毒症时血管内皮损伤的确切机制尚不清楚。 血管内皮表面为糖萼层,由带高度负电荷的含糖胺聚糖（GAGs）侧链的蛋白聚糖组成。脓毒症时糖萼层损伤是内皮屏障破坏的第一步，继而发生内皮细胞水肿、凋亡及脱落，加速脓毒症进展。 研究表明脓毒症时血管内皮损伤标志物GAGs、硫酸肝素、syndecan-1等蛋白聚糖水解产物升高并与脓毒症死亡率密切相关，而内皮表面GAGs侧链的水解由肝素酶（HPA）介导，高糖、低氧等因素均可使血管内皮HPA表达增加，探究脓毒症时内皮屏障破坏与内皮HPA含量之间的关系，并观察使用其抑制剂肝素、PI-88等抑制HPA表达后对内皮功能的影响，初步探讨脓毒症时内皮损伤的机制并寻找可能的治疗靶点具有重要的研究价值。

中文关键词： 脓毒症；内皮；肝素酶；自主神经；血管低反应性

英文摘要： Sepsis will cause endothelium dysfunction and lead to activation of the coagulation cascades and subsequent inflammatory response , such as fluid leakage and vasoparesis, and then may cause septic shock and Multiple Organ Dysfunction Syndrom(MODS). Endothelium injury plays a major role in the occurrence and development of sepsis. More and more researchers have taken endothelium as a theraputic target for sepsis. But the involving mechanism about endothelium dysfunction is still not clear. The vascular endothelium is coated with negatively charged proteoglycan of heparan sulphate(HS) glycosaminoglycan (GAG) chains . The deterioration of the endothelial glycocalix is one of the earliest steps within this scenario that triggers the loss of endothelial barrier function. And it will cause edema, apoptosis,and detachment in endothelial cells and aggravate sepsis, lead to septic shock and MODS. Several investigations have indicated that the concentration of several circulating endothelium injury markers as GAGs, HS ,and syndecan-1 will increase during sepsis , and the increasement is relevant with the severity and mortality of sepsis.Heparanase breaks down heparan sulphate glycosaminoglycan chains . High glucose and low oxygen both can increase the expression of heparanase in endothelial cells.To explore the relation

英文关键词： sepsis；endothelium；heparanase；autonomic nervous；vascular hyporesponsiveness