修饰血红蛋白作为红细胞代用品的研究进展和挑战

血源紧缺和病毒污染问题推动了血液代用品的研究,以血红蛋白为代表的红细胞代用品成为研究的重点。为克服血红蛋白直接使用的毒副作用,各种修饰技术得到了迅速发展,其中包括双阿司匹林交联、戊二醛交联、棉子糖交联、聚乙二醇偶联、脂质体包埋、生物可降解高分子包埋等。其中一些技术已经形成规模化制备工艺,产品进入临床试验,有的已在个别国家上市。鉴于这项研究意义重大,我国有关研究已经起步并正在迅速发展,各国同行的研究有重要的参考价值,因此有必要对近年来血红蛋白作为红细胞的代用品研究状况进行分析,明确面临的挑战,这将有利于发展更全面和有效的研究方案,以期取得突破性进展。

Development and Challenge of Modified Hemoglobins as Red Blood Cell Substitutes

The problems of blood shortage and the virus infection risk of blood transfusion have promoted the study of blood substitutes. Modified hemoglobin has become the focus of the research because of its excellent oxygen carrying ability. To overcome the toxicity effect on direct use of purified native hemoglobin, various modification technologies have been developed, including diaspirin cross-linking, glutaraldehyde polymerization, O-raffinose polymerization, polyethylene glycol conjugation, liposome encapsulation and biodegradable polymer encapsulation. Some of the products have been in clinical trials, and one of the products has been approved in a country for clinical use. Research on red blood cell substitutes in China has also developed fast. This paper provides an overview of the history and current status in development of different hemoglobin-based red blood cell substitutes, especially the problems encountered, the challenges faced, and the prospects in future.