Hemoglobin-vesicles for a Transfusion Alternative and Targeted Oxygen Delivery

Hemoglobin-vesicles for a Transfusion Alternative and Targeted Oxygen Delivery
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用于输血替代方案和定向供氧的血红蛋白囊泡

DOI:
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发表时间:
2007
影响因子:
4.4
通讯作者:
E. Tsuchida
E. Tsuchida
中科院分区:
医学2区
文献类型:
--
作者:
H. Sakai;E. Tsuchida

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Hb囊泡(HbV)是将纯化的Hb溶液(35 g/dl)包封在单层磷脂囊泡(脂质体)中的人工氧载体。HbV的分散稳定性是使用聚乙二醇(PEG)表面改性获得的,使得脱氧的HbV可以在室温下储存多年。此外,静脉内注射的HbV在与血液成分接触时不诱导聚集。动物实验已经验证了HbV作为输血替代品的安全性和有效性。HbV的一个优点是,HbV的O2亲和力(P50)可以很容易地调节到RBC的O2亲和力(28 μ g),并通过操纵HbV中共包封的变构效应物(如吡哆醛5′-磷酸)的量调节到其他值。具有较低P50(较高O2亲和力)的HbV可能将O2保留在正常组织中,同时将O2卸载到靶向缺氧组织。小HbV(直径250-280 nm)均匀分布在血浆相中,并且HbV将通过缺血组织中的侧支动脉运输氧。国内外合作的体外和体内实验结果证实了HbV靶向输送O2的可能性。
Hb-vesicles (HbV) are artificial oxygen carriers that encapsulate purified Hb solution (35 g/dl) in unilamellar phospholipid vesicles (liposomes). The dispersion stability of HbV is attained using surface-modification with polyethylene glycol (PEG), so that the deoxygenated HbV can be stored at room temperature for years. Moreover, the intravenously injected HbV does not induce aggregation when contacted with blood components. Animal experiments have verified the safety and efficacy of HbV as a transfusion alternative. One advantage of HbV is that the O2 affinity (P50) of HbV can be regulated easily to that of RBC (28 torr) and to other values by manipulating the amount of the allosteric effectors, such as pyridoxal 5′-phosphate, coencapsulated in HbV. It is possible that HbV with a lower P50 (higher O2 affinity) would retain O2 in the normal tissue while unloading O2 to a targeted hypoxic tissue. Small HbV (250–280 nm diameter) is distributed homogeneously in the plasma phase, and HbV would transport oxygen through collateral arteries in the ischemic tissues. Results of in vitro and in vivo experiments of the domestic and international collaborations have confirmed the possibility of targeted O2 delivery by HbV.
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通过向小鼠输注高 O2 亲和力重组血红蛋白聚合物来挽救局灶性脑缺血损伤。
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