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新生红细胞的特征、功能及安全性:体内研究

Characteristics of neo red cells, their function and safety: in vivo studies.

作者信息

Ogata Y, Goto H, Sakaguchi K, Suzuki M, Ohsaki K, Suzuki K, Saniabadi A R, Kamitani T, Takahashi A

机构信息

R & D Center TERUMO Corp., Kanagawa, Japan.

出版信息

Artif Cells Blood Substit Immobil Biotechnol. 1994;22(3):875-81. doi: 10.3109/10731199409117924.

Abstract

A new type of artificial oxygen carriers, the Neo Red Cells (NRCs) have been developed and investigated for oxygen transporting efficiency and safety in experimental animals. Stroma free hemoglobin from outdated human red blood cells together with inositol hexaphosphate as an allosteric effector under sterile, pyrogen free condition were encapsulated in liposomes and then were coated with polyethylene glycol bond to hydrogenated soy phosphatidylethanolamine as a surface modifier to prevent aggregation of NRCs in plasma. The efficiency of the NRCs in tissue oxygenation was studied in rabbits which were made severely anemic by drawing 85% of their blood and immediately replacing it with NRC solution. The animals, all recovered to pre-anemic conditions within 6-8 hr and lived normally until being sacrificed, 6 months after the exchange transfusion. The circulation half-life and tissue distribution of NRCs were studied using radiolabeled NRCs. Within the circulation, the half-life of NRCs was 21 hr and extravascularly, they were distributed mainly in and metabolized by the reticuloendothelial system within 7 days. Our observations suggest that the NRCs prepared and investigated in this study are efficient oxygen carriers without causing serious adverse reactions and can be prepared free from pathogenic micro-organisms by special filtration technique before encapsulation of Hb. Currently, experiments are ongoing to control auto-oxidation of oxyHb to metHb which is higher in NRCs than in native red cells at physiological conditions.

摘要

一种新型的人工氧载体——新型红细胞(NRCs)已被研发出来,并在实验动物身上对其氧运输效率和安全性进行了研究。将过期人红细胞中的无基质血红蛋白与作为变构效应剂的肌醇六磷酸在无菌、无热原条件下封装于脂质体中,然后用聚乙二醇与氢化大豆磷脂酰乙醇胺结合作为表面修饰剂进行包被,以防止NRCs在血浆中聚集。通过抽取85%的血液使兔子严重贫血,然后立即用NRC溶液替代所抽血液,以此来研究NRCs在组织氧合方面的效率。所有动物在6 - 8小时内恢复到贫血前状态,并正常存活直至在换血6个月后被处死。使用放射性标记的NRCs研究了其循环半衰期和组织分布。在循环中,NRCs的半衰期为21小时,在血管外,它们主要分布在网状内皮系统中,并在7天内被代谢。我们的观察结果表明,本研究中制备和研究的NRCs是有效的氧载体,不会引起严重不良反应,并且在封装血红蛋白之前可通过特殊过滤技术制备无致病微生物的产品。目前,正在进行实验以控制氧合血红蛋白(oxyHb)在生理条件下自动氧化为高铁血红蛋白(metHb)的过程,这一过程在NRCs中比在天然红细胞中更为明显。

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