2023 Fiscal Year Final Research Report

Cardioprotective effect of lactoferrin via PI3K/Akt pathway against stunned myocardium

Research Project

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Project/Area Number	21K08965
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 55050:Anesthesiology-related
Research Institution	University of Yamanashi
Principal Investigator	Matsukawa Takashi 山梨大学, 大学院総合研究部, 教授 (80209519)
Co-Investigator(Kenkyū-buntansha)	中楯陽介筑波大学, 医学医療系, 講師 (50597002) 小口健史山梨大学, 大学院総合研究部, 准教授 (60201399)
Project Period (FY)	2021-04-01 – 2024-03-31
Keywords	心筋虚血再灌流障害 / ラクトフェリン / 心臓手術 / 人工心肺 / 心収縮力
Outline of Final Research Achievements	Lactoferrin is an iron-binding glycoprotein. Although lactoferrin exhibits organ-protective effects, it is still unclear whether it attenuates myocardial ischemia-reperfusion injury. The purpose of this study was to investigate the effects and mechanism of lactoferrin on myocardial ischemia-reperfusion injury. Hearts were harvested from Wistar rats and perfused using the Langendorff system. The primary outcome was the recovery of cardiac contractility after total cardiac ischemia. Enteral lactoferrin was superior in restoring cardiac contractility after ischemia; the PKA pathway was significantly activated and serum GLP-1 was elevated. In conclusion, enteral lactoferrin induced cardioprotection against myocardial ischemia-reperfusion injury via the PKA signaling pathway and increased serum GLP-1 levels.　Preoperative oral lactoferrin intake may be cardioprotective against ischemia-reperfusion injury in cardiac surgery patients.
Free Research Field	麻酔
Academic Significance and Societal Importance of the Research Achievements	今日、手術技術の向上、モニター・麻酔薬の開発などにより、より多くの患者が人工心肺を用いた心臓手術を受けている。しかし、心臓手術では人工心肺装置による炎症反応の惹起・心停止による虚血再灌流障害に起因する術後心不全など合併症率が高い。心筋虚血再灌流障害に対しては、吸入麻酔やオピオイドを用いた薬理学的プレコンディショニングによる心筋保護が臨床的に使用されているが、その効果は限定的である。今回の研究で経口ラクトフェリン投与の有効性が明らかになり、心臓手術患者の心筋保護戦略となることが期待される。