| Project/Area Number |
17H02087
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biomedical engineering/Biomaterial science and engineering
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| Research Institution | Nara Medical University |
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Principal Investigator |
SAKAI HIROMI 奈良県立医科大学, 医学部, 教授 (70318830)
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| Co-Investigator(Kenkyū-buntansha) |
松平 崇 奈良県立医科大学, 医学部, 助教 (20570998)
山本 惠三 奈良県立医科大学, 医学部, 准教授 (90254490)
山田 孫平 奈良県立医科大学, 医学部, 研究員 (90839317)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥17,810,000 (Direct Cost: ¥13,700,000、Indirect Cost: ¥4,110,000)
Fiscal Year 2019: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2018: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2017: ¥8,710,000 (Direct Cost: ¥6,700,000、Indirect Cost: ¥2,010,000)
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| Keywords | 人工臓器学 / 人工赤血球 / リポソーム / 輸血代替 / 電子伝達系 / 蘇生液 / 輸液 / ヘモグロビン / 解糖系酵素 / NADH / メチレンブルー / 一酸化炭素 / 酸素輸送 / 虚血 / 酸化ストレス / 人工臓器 |
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| Outline of Final Research Achievements |
Artificial red cells (HbV) are being developed as a transfusion alternative. To prolong the functional life span of HbV in blood circulation by preventing metHb formation, we studied two approaches. We clarified that coexistence of NADH with HbO2 induces pseudo-catalase and pseudo-SOD activities by stoichiometric interaction of NADH with alpha chain of HbO2, and retards metHb formation. Also we established an indirect enzymatic metHb reducing system by extracting glycolytic energies produced in erythrocytes using methylene blue (MB) and other phenothiazine dyes in circulating blood, and found out better dyes than MB, such as Azure B. Carbon monoxide-bound HbV releases CO and mitigates oxidative and inflammatory diseases. We clarified that the released CO does not seem to influence the cranial nervous system. The results will contribute to the improvement of functional lifespan of HbV and also application to other diseases in addition to its usage as a transfusion alternative.
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| Academic Significance and Societal Importance of the Research Achievements |
人工赤血球(HbV)は、感染源、血液型を含まず、長期保存ができ、現行の献血-輸血技術を補完する製剤として期待されている。本研究の成果は、人工赤血球製剤の投与後の酸化劣化を遅延させて酸素運搬機能の向上をもたらすこと、またCO徐放効果も含めて様々な疾患の治療への応用につながると考えら得る。また、学術的観点から、まず１）赤血球解糖系エネルギーを活用して化学反応に用いる新しい考えを構築したこと、２）補酵素として知られるNADHについて赤血球内における新しい役割を提案できたこと、そして3)毒ガスCOの生体内における有用性と安全性が明らかになりつつあることを意義として挙げることができる。
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