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

本项目的目的是阐明血红蛋白囊泡（HbV）悬浮液对缺血组织氧合的机制和优化。HbV的一个优点是Hb的O_2亲和力（P_<50>）可以很容易地通过操纵HbV共包的变张效应物来调节。一个概念是，低P_<50>的HbV会将O_2保留在正常组织中，同时将O_2卸载到目标缺氧组织。HbV （P_<50> =9 mmHg）增强了仓鼠背侧皮瓣缺血部分的氧合，使组织O_2张力显著降低。注射HbV增加血浆黏度，从而增强血管舒张，从而恢复经侧支动脉的血流量和供氧。在另一项实验中，与正常P_<50> HbV相比，低P_<50> HbV在闭塞的小动脉中表现出较慢的O_2卸载。低P_<50>的HbV作为O_2供应来源的贡献即使在小剂量的HbV下也超过了RBC，这表明HbV可能用于O_2治疗。这些发现表明，操纵乙肝病毒的物理化学性质可以为许多临床适应症使用量身定制的人工氧载体。

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.