Is the PDE5 inhibitor tadalafil an innovative treatment for renal ischemia reperfusion injury?

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K09711
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56030:Urology-related
• Research Institution: Okayama University
• Principal Investigator: Motoo Araki 岡山大学, 医歯薬学域, 教授 (90467746)
• Co-Investigator(Kenkyū-buntansha): 城所 研吾 川崎医科大学, 医学部, 講師 (50435020)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: 腎移植 / 腎虚血再灌流障害

Outline of Final Research Achievements

Both WT and eNOS-KO mice showed significant reduction of tubular damage after tadalafil treatment. Flow cytometry in the kidneys showed that the percentage of neutrophils in renal tissue was significantly reduced in tadalafil-treated mice, both WT and eNOS-KO mice; in vivo imaging showed a stronger accumulation of neutrophils entering the glomeruli at 1 hour in eNOS-KO mice than in WT mice, and a greater number of neutrophils migrating into the tubules at 3 hours. neutrophils into the tubules at 3 hours. Oral tadalafil reduced neutrophil influx into the glomerulus, more pronounced in eNOS-KO. In addition, the percentage of neutrophil-positive volume in the glomerulus at 1 hour after reperfusion was significantly higher in eNOS-KO than in WT, and both were reduced with tadalafil.

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Free Research Field

腎移植

Academic Significance and Societal Importance of the Research Achievements

腎虚血再灌流障害の新たな研究手法として2光子レーザー顕微鏡を用いたイメージング技術を駆使することで、世界に先駆けて生体マウス腎において好中球in vivo イメージングに成功した。これにより、好中球の糸球体への流入・血管内rollingを捉える事が可能となり、さらなる病態解明に寄与できる。今回、局所での好中球浸潤がタダラフィルにより抑制されることが確認できた。腎組織内の微小環境の変化をダイナミックに直接可視化できるこのイメージング技術は、腎臓に留まらない、様々な臓器における疾患の病態基盤の解明に有用であると考えられる。本研究の成果から、tadalafilが治療候補となり得る可能性が示唆された。