Artificial Red Cells : Physiological Importance of the Ligand Reaction Dynamism and the New Application for Ligand Therapy

人工红细胞：配体反应动力学的生理重要性和配体治疗的新应用

• 批准号: 19300164
• 负责人: SAKAI Hiromi
• 金额: $ 12.31万
• 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: 2007
• 资助国家: 日本
• 起止时间: 2007 至 2009
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-19300164/
• 关键词: 人工臓器工学; 人工赤血球; 生体材料; 生物・生体工学; ナノバイオ; 生体機能利用; 人工血液; 一酸化窒素; 一酸化炭素; レオロジー

Chemically modified hemoglobin (Hb) solutions as artificial O_2 carriers show vasoconstriction and hypertension presumably due to the high affinity for endogenous NO and CO as vasorelaxation factors, and due to the faster O_2-release that induces autoregulatory vasoconstriction. On the other hand, cellular-type Hb-vesicle (HbV) does not induce such side effects. Herein we analyzed the reactions of ligand gaseous molecules by physicochemical techniques, and found out that HbV shows much slower reactions and it is due to the intracellular gas diffusion barrier induced by a concentrated Hb solution, and the retarded lateral diffusion of HbV when it flows in a narrow tube. In addition, we tested HbV as an exogenous CO carrier because endogenous CO is cytoprotective. After inducing hemorrhagic shock, rats were resuscitated with CO-bound HbV. It showed cytoprotective effect at reperfusion, and CO was dissociated rapidly and exhaled through the lung. No symptom related to toxicity of CO was detected. The results imply the possibility of artificial red cells for a new ligand therapy.

化学修饰血红蛋白（Hb）溶液作为人工O_2载体表现出血管收缩和高血压，可能是由于内源性NO和CO作为血管松弛因子的高亲和力，以及由于更快的O_2释放诱导自调节性血管收缩。另一方面，细胞型乙型肝炎囊泡（HbV）不会引起这种副作用。本文通过物理化学技术分析了配体气体分子的反应，发现HbV的反应速度要慢得多，这是由于高浓度Hb溶液在细胞内形成气体扩散屏障，以及HbV在窄管中流动时，其横向扩散受到阻碍。此外，我们测试了HbV作为外源性CO载体，因为内源性CO具有细胞保护作用。在引起失血性休克后，用co结合HbV对大鼠进行复苏。在再灌注时表现出细胞保护作用，CO迅速解离，经肺呼出。未发现与一氧化碳毒性相关的症状。这一结果暗示了人造红细胞作为一种新的配体疗法的可能性。

项目成果

Effect of hemoglobin vesicles, cellular-type artificial oxygen carriers, on the ex vivo expansion of human hematopoietic stem/progenitor cells using a coculture system with human stromal cells

血红蛋白囊泡、细胞型人工氧载体对使用与人类基质细胞共培养系统的人类造血干/祖细胞的离体扩增的影响

• 发表时间: 2009
• 期刊: ASA1O J. 55
• 作者: M.Yamaguchi;et al.
• 通讯作者: et al.

人工酸素運搬体.「からだと酸素の事典」酸素ダイナミクス研究会編.第5章:酸素の利用.pp.478-484

人工氧载体。氧气动力学研究组编辑的《身体和氧气百科全书》第5章：氧气的利用。

• 发表时间: 2009
• 作者: 堀之内宏久;小林紘一;酒井宏水;土田英俊
• 通讯作者: 土田英俊

Pharmacokinetic Study of Enclosed Hemoglobin and Outer Lipid Component after the Administration of Hemoglobin Vesicles as an Artificial Oxygen Carrier

• DOI: 10.1124/dmd.109.027094
• 发表时间: 2009-07-01
• 期刊: DRUG METABOLISM AND DISPOSITION
• 影响因子: 3.9
• 作者: Taguchi, Kazuaki;Urata, Yukino;Otagiri, Masaki
• 通讯作者: Otagiri, Masaki

Hemoglobin encapsulation in vesicles retards NO- and CO-bindings and O2-release when perfused throughnarrow gas-permeable tubes

当通过狭窄的透气管灌注时，血红蛋白封装在囊泡中会延迟 NO 和 CO 的结合以及 O2 的释放

• 发表时间: 2010
• 期刊: Am.J.Physiol.Heart Circ.Physiol. 298
• 作者: H.Sakai;N.Okuda;A.Sato;S.Takeoka;E.Tsuchida.
• 通讯作者: E.Tsuchida.

Effects of hemoglobin vesicles, a cellular-type artificial oxygen carrier, on human hematopoietic stem/progenitor eells in vitro.

血红蛋白囊泡（一种细胞型人工氧载体）对体外人造血干/祖细胞的影响。

• 发表时间: 2009
• 期刊: J. Biomed. Materials Res. 88A
• 作者: M. Yamaguohi;M. Fujihara;S. Wakamoto;H. Sakai;et al.
• 通讯作者: et al.