Abe Hideki, Azuma Hiroshi, Yamaguchi Miki, Fujihara Mitsuhiro, Ikeda Hisami, Sakai Hiromi, Takeoka Shinji, Tsuchida Eishun
Hokkaido Red Cross Blood Center, Sapporo, Japan.
Artif Cells Blood Substit Immobil Biotechnol. 2007;35(2):157-72. doi: 10.1080/10731190601188224.
Hemoglobin vesicle (HbV), a liposomal oxygen carrier containing human hemoglobin, was intravenously infused into rats. After the infusion of saline, the HbV or empty vesicle (EV), numbers of red cells, leukocytes and platelets in peripheral blood were unchanged during the observation period of one week in addition to each time point among three groups. However, the lymphocyte ratio transiently decreased and the granulocyte ratio increased in the HbV and EV groups at 6 h after the infusion. Those changes returned to the initial value one day after the infusion and those were maintained for the subsequent observation period. No dramatic change was seen in the ratio of CD4(+)/CD8(+) T cells. A transient decrease of the complement titer was observed three days after the infusion of HbV and EV, although the consumption of complement titer was not detected in rat serum by mixing HbV or EV in vitro, indicating that the transient decrease of complement titer in vivo was not due to the consumption of complement due to the interaction with HbV or EV. Multiple infusions of HbV caused the decrease of complement titer only after the first infusion and no allergic reaction was observed. No anaphylactic shock was observed in rats administered with EV several times, while ovalbumin (OVA) sensitized rats died with symptoms of respiratory distress after the second OVA administration. These results indicate that HbV could be administered without serious clinical symptoms or adverse reactions.
将含有人血红蛋白的脂质体氧载体血红蛋白囊泡（HbV）静脉注入大鼠体内。在输注生理盐水、HbV或空囊泡（EV）后，三组中每个时间点以及在一周的观察期内，外周血中的红细胞、白细胞和血小板数量均无变化。然而，输注后6小时，HbV组和EV组的淋巴细胞比例短暂下降，粒细胞比例升高。这些变化在输注后一天恢复到初始值，并在随后的观察期内保持不变。CD4(+)/CD8(+) T细胞比例未见明显变化。输注HbV和EV三天后观察到补体滴度短暂下降，尽管在体外将HbV或EV与大鼠血清混合未检测到补体滴度的消耗，这表明体内补体滴度的短暂下降并非由于与HbV或EV相互作用导致补体消耗所致。多次输注HbV仅在首次输注后导致补体滴度下降，未观察到过敏反应。多次给予EV的大鼠未观察到过敏性休克，而卵清蛋白（OVA）致敏的大鼠在第二次给予OVA后因呼吸窘迫症状死亡。这些结果表明，HbV给药后不会出现严重的临床症状或不良反应。
