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血红蛋白-白蛋白聚集体“HemoAct”作为红细胞替代物的安全性评估。

Safety Evaluation of Hemoglobin-Albumin Cluster "HemoAct" as a Red Blood Cell Substitute.

作者信息

Haruki Risa, Kimura Takuya, Iwasaki Hitomi, Yamada Kana, Kamiyama Ikuo, Kohno Mitsutomo, Taguchi Kazuaki, Nagao Saori, Maruyama Toru, Otagiri Masaki, Komatsu Teruyuki

机构信息

Department of Applied Chemistry, Faculty of Science and Engineering, Chuo University, 1-13-27 Kasuga, Bunkyo-ku, Tokyo 112-8551, Japan.

Department of Thoracic Surgery, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.

出版信息

Sci Rep. 2015 Jul 29;5:12778. doi: 10.1038/srep12778.

DOI:10.1038/srep12778
PMID:26220366
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4518235/
Abstract

A hemoglobin (Hb) wrapped covalently by human serum albumins (HSAs), a core-shell structured hemoglobin-albumin cluster designated as "HemoAct", is an O2-carrier designed for use as a red blood cell (RBC) substitute. This report describes the blood compatibility, hemodynamic response, and pharmacokinetic properties of HemoAct, and then explains its preclinical safety. Viscosity and blood cell counting measurements revealed that HemoAct has good compatibility with whole blood. Intravenous administration of HemoAct into anesthetized rats elicited no unfavorable increase in systemic blood pressure by vasoconstriction. The half-life of (125)I-labeled HemoAct in circulating blood is markedly longer than that of HSA. Serum biochemical tests conducted 7 days after HemoAct infusion yielded equivalent values to those observed in the control group with HSA. Histopathologic inspections of the vital organs revealed no marked abnormality in their tissues. All results indicate that HemoAct has sufficient preclinical safety as an alternative material for RBC transfusion.

摘要

一种由人血清白蛋白（HSA）共价包裹的血红蛋白（Hb），即一种被命名为“HemoAct”的核壳结构血红蛋白-白蛋白聚集体，是一种被设计用作红细胞（RBC）替代物的氧载体。本报告描述了HemoAct的血液相容性、血流动力学反应和药代动力学特性，然后解释了其临床前安全性。粘度和血细胞计数测量结果显示，HemoAct与全血具有良好的相容性。将HemoAct静脉注射到麻醉大鼠体内不会因血管收缩而导致全身血压出现不利升高。循环血液中（125）I标记的HemoAct的半衰期明显长于HSA。HemoAct输注7天后进行的血清生化测试结果与HSA对照组观察到的值相当。重要器官的组织病理学检查显示其组织无明显异常。所有结果表明，HemoAct作为RBC输血的替代材料具有足够的临床前安全性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4a4/4518235/2d1b3bcedfa8/srep12778-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4a4/4518235/91bd1439d989/srep12778-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4a4/4518235/39f7b2947271/srep12778-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4a4/4518235/dc0d43c0f289/srep12778-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4a4/4518235/6b273e8df5f3/srep12778-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4a4/4518235/e1f3a67d693a/srep12778-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4a4/4518235/2d1b3bcedfa8/srep12778-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4a4/4518235/91bd1439d989/srep12778-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4a4/4518235/39f7b2947271/srep12778-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4a4/4518235/dc0d43c0f289/srep12778-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4a4/4518235/6b273e8df5f3/srep12778-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4a4/4518235/e1f3a67d693a/srep12778-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4a4/4518235/2d1b3bcedfa8/srep12778-f6.jpg

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