2019 Fiscal Year Final Research Report
Analysis of novel mechanism of prevention of lipid peroxidation dependent cardio sudden death by antibiotic induced changes of intestinal bacteria
Project/Area Number |
17K08285
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Biological pharmacy
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Research Institution | Kitasato University |
Principal Investigator |
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Project Period (FY) |
2017-04-01 – 2020-03-31
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Keywords | 抗生物質 / 腸内細菌 / 心不全 / 脂質酸化依存的新規細胞死 / ビタミンE / 無菌マウス / ノトバイオート |
Outline of Final Research Achievements |
The heart-specific GPx4 knockout mouse can survive by the vitamin E supplementation diet, but lipid peroxidation-dependent novel cell death is induced in cardiomyocytes by decrease of vitamin E in heart after change to low vitamin E containing diet, resulting in cardio sudden death. We found antibiotic cefoperazone(CPZ) as the non-antioxidant compound which can suppress this lipid peroxidation-dependent heart failure by drinking, but not intraperitoneal injection. Administration of antibiotic CPZ could not rescue lipid peroxidation dependent cardio sudden death in germ free mice. Next generation sequencer and bacteria transplantation experiment revealed that antibiotic CPZ resistant intestinal bacteria could suppress lipid peroxidation dependent cardio sudden death in heart-specific GPx4 knockout mouse.
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Free Research Field |
脂質生化学、衛生薬学、栄養学
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Academic Significance and Societal Importance of the Research Achievements |
本研究では、脂質酸化依存的におきる心不全を抑制できるCPZ耐性腸内細菌が存在することを初めて明らかにした。また抗生物質CPZにより生き残った腸内細菌が機能を発揮したことから抗生物質の新たな可能性を示したともいえる。本研究成果は腸内細菌Zが心臓機能を正に制御できること、新しい腸―心連関が存在することを示したことになり学術的意義は極めて大きい。将来的に心臓機能を増強できるプロバイオティクスやプレバイオティクスの開発や心臓突然死の予防薬の開発に繋がる研究成果である。
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