2022 Fiscal Year Final Research Report
Tetrahydrobiopterin in sepsis associated encephalopathy and its consideration as a therapeutic target.
Project/Area Number |
19K09438
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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 |
Review Section |
Basic Section 55060:Emergency medicine-related
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Research Institution | Kagoshima University |
Principal Investigator |
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Co-Investigator(Kenkyū-buntansha) |
伊藤 隆史 熊本大学, 大学院生命科学研究部(保), 教授 (20381171)
原 怜 東京工業大学, 生命理工学院, 助教 (70624815)
安田 智嗣 鹿児島大学, 医歯学総合研究科, 客員研究員 (80437954)
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Project Period (FY) |
2019-04-01 – 2023-03-31
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Keywords | 敗血症 / テトラヒドロビオプテリン / 敗血症関連脳症 / アミノ酸代謝 |
Outline of Final Research Achievements |
The purpose of this study was to elucidate the involvement of BH4 in the pathogenesis of sepsis-related encephalopathy and to examine its preventive effect and prognosis. We found that an increase in BH2, an oxidized form of BH4, is involved in vascular endothelial cell damage, and that early inhibition of oxidation improves prognosis. Analysis of BH4, BH2, and phenylalanine (Phe) in blood and brain tissue, and histological evaluation of the brain showed that all changes were maximal at 24 hours after CLP and did not recover even at 96 hours. In a clinical study of septic patients admitted to the ICU, increased BH4, BH2, Phe, and tyrosine and decreased arginine at the beginning of admission were observed. However, in the present analysis, no association was found between these changes and the development of encephalopathy.
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Free Research Field |
敗血症
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Academic Significance and Societal Importance of the Research Achievements |
敗血症関連脳症の発症メカニズムはまだ十分解明されておらず、我々の研究によってBH4の関与が示唆されたことは、予防的観点からも重要なことであると考える。敗血症の急性期における過剰なBH4、NOは血液浄化療法によって除去できることがわかっているが、BH4に関しては一方的な除去だけでなく濃度コントロールの必要性を意識した治療介入が重要であり、さらに今後は、BH4の不足した細胞に必要量のBH4を届ける方法についての検討が必要である。
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