心筋障害部位での超急性期の代謝の継時的な変化をとらえるために、マイクロダイアラシス法を用いた技術の開発を行った。Wistarラットの左室心筋局所に ダイアリシスプロープを植え込んで、インジェクションポンプを用いて灌流し、終端より環流液を回収し、質量分析法で代謝産物を網羅的に解析した。虚血時および再還流時に、細胞外のグルタチオン関連物質の有意な変動が明らかになった。心筋培養細胞でも、虚血再酸素化時に、グルタチオンの細胞外への放出が増大し、細胞内の活性酸素、過酸化脂質が経時的に増大した。またグルタチオンの投与は、細胞内のグルタチオン濃度を保持し、虚血再酸素化時の細胞障害を抑制した。
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.

研究種目 : 若手研究
研究期間 : 2019～2021
課題番号 : 19K17579
研究分野 : 循環器内科