"Analysis of oxygen releasing behavior of hemoglobin-vesicles (nano-particles) and the mechanism of oxygenation of ischemic tissue."

“分析血红蛋白囊泡（纳米颗粒）的释氧行为和缺血组织的氧合机制。”

• 批准号: 16300162
• 负责人: SAKAI Hiromi
• 金额: $ 9.54万
• 依托单位: Waseda University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16300162/
• 关键词: Artificial Red Cells; Microcirculation; Hemoglobin; Ischemia; Oxygen release; Hemorheology; Artificial Blood; Liposome; レオロジー制御; 輸血代替

The purpose of this project was to clarify the mechanism and optimization of oxygenation of ischemic tissues by a suspension of hemoglobin-vesicles (HbV). One advantage of HbV is that O_2 affinity (P_<50>) of Hb can be easily regulated by manipulating the allosteric effectors coencapsulated in HbV. One concept is that the low P_<50> HbV would retain O_2 in the normal tissue while unloading O_2 to a targeted hypoxic tissue. HbV (P_<50> =9 mmHg) enhanced oxygenation of an ischemic part of hamster dorsal skin flap where tissue O_2 tension was significantly reduced. Injection of HbV increased the plasma viscosity, thus enhance the vasorelaxation and the resulting recovery of blood flow and oxygen delivery via collateral artery. In another experiment, low P_<50> HbV showed slower O_2 unloading in the occluded arterioles in comparison with normal P_<50> HbV. The contribution of the low P_<50> HbV as the source of O_2 supply exceeds that of RBC even with a small dosage of HbV, indicating the possible utilization of HbV for O_2 therapeutics. These findings indicates that manipulation of the physicochemical properties of HbV enables possible use of tailor-made artificial oxygen carriers for many clinical indications.

本项目的目的是阐明血红蛋白-囊泡(HBVs)悬浮液对缺血组织氧合的机制和优化。乙肝病毒的一个优点是，通过操纵乙肝病毒共包裹的变构效应，可以很容易地调节Hb的氧亲和力(P&lt；50&gt；)。一种概念是，低P&lt；50&gt；乙肝病毒会在正常组织中保留氧气，同时将氧气卸载到靶向缺氧组织。乙肝病毒(P&lt；50&gt；=9 mm Hg)可显著降低组织氧分压，增强地鼠背侧皮瓣缺血区的氧合作用。注射乙肝病毒使血浆粘度升高，从而增强血管的松弛，恢复侧支动脉的血流量和氧气输送。在另一项实验中，与正常的P&lt；50&gt；乙肝病毒相比，低P&lt；50&gt；乙肝病毒在闭塞的小动脉中表现出较慢的O2卸载。低P_(50)&gt；乙肝病毒作为氧源的贡献，即使在小剂量的乙肝病毒作用下也超过红细胞，提示乙肝病毒在氧疗中有可能被利用。这些发现表明，通过操纵乙肝病毒的物理化学性质，可以在许多临床适应症中使用定制的人造氧气载体。

项目成果

Oxygen Infusions(Hemoglobin-Vesicles and Albumin-Hemes) Based on Nano-Molecular Sciences

基于纳米分子科学的氧气输注（血红蛋白-囊泡和白蛋白-血红素）

• 发表时间: 2005
• 期刊: Polym. Adv. Technol. 16
• 作者: E. Tsuchida;H. Sakai;T. Komatsu;S. Takeoka;Y. Huang;K. Sou;A. Nakagawa;Y. Teramura;K. Kobayashi
• 通讯作者: K. Kobayashi