Specialized pro-resolving lipid mediators in an experimental model of lung transplantation

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K24011
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0905:Surgery of the organs maintaining homeostasis and related fields
• Research Institution: Kyoto University
• Principal Investigator: Tanaka Satona 京都大学, 医学研究科, 助教 (80847517)
• Project Period (FY): 2019-08-30 – 2021-03-31
• Keywords: 虚血再灌流障害 / 肺移植 / 抗炎症性脂質メディエーター

Outline of Final Research Achievements

Specialized pro-resolving lipid mediators (SPMs), which are produced from Arachidonic acid, Docosahexaenoic acid, and Eicosapentaenoic acid in vivo to resolve inflammation, have been identified. To investigate the role of SPMs in pulmonary ischemia-reperfusion injury, we utilized a hilar clamp model in rat, where the blood supply and ventilation are intercepted by occluding left hilum and then reperfusion is resumed by releasing the occlusion to induce acute lung injury. In this experimental model of pulmonary ischemia-reperfusion injury, Aspirin-triggered Resolvin D1 and Aspirin-triggered Lipoxin A4 agonistic to FPR2 receptor attenuated acute lung injury with improved lung physiology and anti-inflammatory effect.

Free Research Field

肺移植

Academic Significance and Societal Importance of the Research Achievements

虚血状態におかれた肺に換気と血流が再開されることにより発症する虚血再灌流肺障害は、肺移植後においては早期の主要な死亡原因のみならず、移植肺の長期成績に影響する。その肺障害の要因は過度な炎症であることが報告されている。今回、申請者は、FPR2受容体に作用するAspirin-triggered Resolvin D1と、Aspirin-triggered Lipoxin A4が虚血再灌流肺障害肺障害に対して保護効果をもたらすことを明らかにした。本研究は、虚血再灌流肺障害における過度な炎症を抑制し臓器を保護するの新たな治療法の提案の基礎になる可能性がある。