HBOCs修饰的研究进展  

Research progress of the modification of HBOCs

作　　者：周文涛[1] 刘嘉馨[1] 王红[1] 杨成民[1] 

机构地区：[1]中国医学科学院北京协和医学院输血研究所,四川成都610052

出　　处：《中国输血杂志》2015年第1期90-94,共5页Chinese Journal of Blood Transfusion

基　　金：国家"863"计划(2012AA021903);四川省科技支撑计划项目(2013SZ0059);四川省技术创新工程专项(2013ZZ0006);四川省国际合作与交流研究计划(2014HH0065)

摘　　要：Hb为基础的载氧药物(HBOCs)在输血治疗中表现出的优势在于能够缓解血液来源短缺,长期保存,降低传播病毒的风险。血红蛋白(Hb)为四亚基蛋白,在体外会迅速分解为二聚体或者单体,迅速经肾脏排出体外,这不仅影响疗效还具有潜在的生理毒性。因此,HBOCs需要解决的关键难点之一就是修饰Hb亚基去除Hb解离所带来的毒性,并有效延长Hb在血管内的半衰期。其有效的反应位点为Hb表面的赖氨酸残基,氨基末端,2,3-DPG的结合位点等,目前国内外常用的修饰剂为羧酸醛类,磷酸吡哆醛类,双阿司匹林,聚乙二醇类等。反应活性受到外界微环境、反应剂的活性等众多因素的影响。Hemoglobin based on oxygen carriers （HBOCs） provides several advantages in alleviating the blood short- age, preserving for a long time, reducing the risk of viral transmission during transfusion. Hemoglobin （Hb）, a tetrameric protein, rapidly dissociates into subunits in extracellular condition. These subunits are then rapidly excreted by the kidney, affecting the efficacy and harboring potential toxicity. Therefore, to resolve one of the key challenges on HBOCs, the modi- fied subunit of Hb can relieve the potential toxicity and prolong the half-lives of HBOCs in the blood vessels. The effective re- spouse sites of Hb include lysine residues on the surface of Hb, amino terminal and 2,3-DPG binding site. Cross-linking a- gents commonly used currently are carboxylic aldehydes, pyridoxal phosphate, bis （3,5-dibromosalicyl） fumarate, （DBBF）, polyethylene glycol, etc. The reaction activity is influenced by many factors such as extemal microenvironment, activity of reactant and others.

关 键 词：HB 四亚基蛋白 载氧药物 修饰 

分 类 号：R457.11[医药卫生—治疗学]