2021 Fiscal Year Final Research Report
Development of in vivo four-dimensional [4D] metabolism imaging
| Project/Area Number |
19K17579
|
|---|
| Research Category |
Grant-in-Aid for Early-Career Scientists
|
| Allocation Type | Multi-year Fund |
|---|
| Review Section |
Basic Section 53020:Cardiology-related
|
|---|
| Research Institution | Keio University |
|---|
Principal Investigator |
|
|---|
| Project Period (FY) |
2019-04-01 – 2022-03-31
|
| Keywords | メタボローム / 虚血再灌流 / 代謝 / マイクロダイアライシス |
|---|
| Outline of Final Research Achievements |
A microdialysis method was developed to capture the metabolic sequential changes during the hyperacute phase at the site of myocardial injury. A dialysate rope was implanted in the left ventricular myocardium of Wistar rats, perfused with an infusion pump, and the annulus fluid was collected from the tip for comprehensive analysis of metabolic products using mass spectrometry. The products were analyzed exhaustively by mass spectrometry. Significant variations in extracellular glutathione-related substances were revealed during ischemia and during reflux. In cultured cardiomyocytes, extracellular glutathione release increased during ischemia and reoxygenation, and intracellular reactive oxygen species and lipid peroxide increased over time. Intracellular glutathione levels were also maintained by glutathione administration, and cellular damage during ischemia and reoxygenation was suppressed.
|
| Free Research Field |
循環器内科
|
| Academic Significance and Societal Importance of the Research Achievements |
虚血再灌流における詳細なRedox代謝変化を検証するため、空間的および時間的な網羅的代謝解析技術を確立した。マイクロ波による心臓処理を行うことで代謝産物の死後のdegradationを完全に抑制し、虚血再灌流時のRedox代謝産物の局在の可視化（マッピング）に成功した。さらに、虚血および再灌流に伴い、ダイナミックに変化する代謝産物の推移を時間軸で把握するために、メタボローム解析とマイクロダイアリシス法を組み合わせた、同一個体で心筋細胞外の代謝変化を連続的に測定する手法を確立した。これらの手法を組み合わせた代謝4次元マッピングは代謝物の時間的変化を明らかにした点に特色を有する。
|
