人工氧载体研究进展

Artificial Oxygen Carriers

血液需求的激增和异体输血的不安全性等问题的出现,促使人们合成"血液替代品"。通过对天然氧载体(即血红蛋白)结构与性能的清晰认识,已有多种人工氧载体被成功合成,并应用于临床试验。人工氧载体可分为全氟碳化合物、血红蛋白基氧载体、合成血红素及其高分子配合物三大类。全氟碳化合物虽大部分已退出人工血液市场,但因其具有治疗作用,研究工作仍在进行。为了降低血红蛋白基氧载体的副作用,已采用多种方法对血红蛋白进行改性,如采用化学修饰、微囊包裹(HbV)、重组和仿生纳米等技术。其中,血红蛋白囊泡模拟红细胞的结构,其粒径相对较大(250nm),副作用相对较低,是目前血红蛋白基氧载体的发展趋势。人工合成血红素如栏式卟啉只溶于有机溶剂,为增加其水溶性,可使其与白蛋白、木糖醇酶和环糊精等高分子结合为配合物,经动物实验表明,这些高分子金属配合物在体内具有运送氧气功能。除主要在临床上用作血液代替品外,人工氧载体还在肿瘤治疗、器官移植和缺血/再灌注损伤的预防等方面具有重要的临床应用价值。

Because of the increasing demand for blood and the emergence of unsafe issues in allogeneic blood transfusion,blood substitutes are attracting increasing interest in chemistry and medical science.Based on the knowledge of the structure and functions of hemoglobin—a typical natural oxygen carrier,many artificial oxygen carriers have been synthesized and applied to clinical trails.Artificial oxygen carriers include perfluorocarbon,hemoglobin-based oxygen carrier,synthetic heme and its polymer metal complexes.Although most of the perfluorocarbons could not be applied as blood substitutes,their applications as medicine are still continued because of their therapeutic effect.In order to reduce unwanted side-effects of hemoglobin-based oxygen carriers,hemoglobin has been modified by many methods,such as chemical modification,microencapsulation,recombinant technology,biomimetic nanotechnology,etc.Among all of the above hemoglobin-based oxygen carriers,the particle size of hemoglobin vesicles（HbV） is relatively larger in the simulation of the structure of the red blood cell.It represents one of the tendency of the progress of hemoglobin-based oxygen carriers.Most of synthetic hemes,such as pocket porphyrin metal complexes,are only dissolved in organic solvents.In order to increase theirwater-solubility,synthetic hemes have been conjugated with albumin,xylitol enzymes and cyclodextrin and so on.The results of animal trial showed that these polymer metal complexes could transport dioxygen in the animal body.Beside to be used as the blood substitutes in clinical trails,artificial oxygen carriers have other potential clinical uses,such as cancer therapy,organ transplantation and prevention of ischemia/reperfusion injury of tissues and organs.