肺移植における第３群肺高血圧症の検討：NCXの関与と新規治療標的としての可能性

肺移植中第 3 组肺动脉高压的检查：NCX 的参与以及作为新治疗靶点的可能性

• 批准号: 19K18230
• 负责人: 永田 旭
• 金额: $ 2.75万
• 依托单位: University of Occupational and Environmental Health, Japan (2021)Fukuoka University (2019-2020)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Early-Career Scientists
• 财政年份: 2019
• 资助国家: 日本
• 起止时间: 2019-04-01 至 2022-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-19K18230/
• 关键词: 肺高血圧; NCX; 肺移植; 第3群肺高血圧症; イオン輸送体

肺高血圧症(PH)は肺動脈圧の持続的上昇とそれに引き続く右心不全を生じる予後不良疾患群で、病態・病因に応じて5群に分類される。研究代表者の前所属施設は国内10施設の肺移植実施施設の一つであり、診療対象の肺移植候補患者は第3群に分類される「肺疾患に伴うPH」をしばしば合併している。第3群PHの悪化はときに末期呼吸不全患者の致命的経過の引き金となりうるため、その制御は待機中死亡の低減と肺移植への到達機会の増加に寄与しうるが、特に薬物的な制御に関しては定まった知見は少ない。本研究では、肺移植適応患者の臨床データ及び摘出肺組織を用いて、近年肺高血圧発症・悪化における役割に注目がなされ、治療標的分子としても期待されているナトリウム-カルシウム交換体(NCX)と第3群PHとの関連を解明し、新規治療薬の開発の一助とすることを目的とした。令和3年度は過年度に集積・解析した臨床データより得られた第3群肺高血圧症の存在が移植待機中患者の予後に影響を及ぼす可能性についての論文作成予定であったが、研究代表者の年度途中の施設異動により、想定していたエフォートを研究に裂くことが困難となった。また、すべての臨床データ・標本データが前所属施設に帰属していることにより、異動先の施設での研究継続が事実上不可能となった。肺移植後摘出組織の一般的形態評価(HE染色やEVG染色)や免疫組織化学的評価（抗体染色）、ならびに画像解析ソフトによる肺高血圧病変(筋性化動脈など）の定量的評価も予定していたがそれらも異動に伴い実施できておらず、今後も実施不可能であると判断し、研究廃止に至った。

Pulmonary hypertension (PH) is a disease caused by a persistent increase in pulmonary artery pressure. The lung transplant candidate patients of the 10 lung transplant facilities in China, to which the representative of the study belongs, are classified into the third group: "lung disease with PH". Group 3: Deaths in patients with terminal respiratory insufficiency due to PH and mortality in patients with terminal respiratory insufficiency due to increased chance of reaching lung transplantation due to increased risk of death and mortality due to increased risk of lung transplantation due to increased risk of death due to increased risk of lung transplantation due to increased risk of death due to increased risk of lung transplantation due to increased risk of death due to increased risk of lung transplantation due to increased risk of death due to increased risk of lung transplantation due to increased risk of lung transplantation due to increased risk of death due to increased risk of lung transplantation due to increased risk of lung transplantation due to increased risk of death due to increased risk of death due to increased risk of lung transplantation due to increased risk of death due to increased risk of lung transplantation due to increased risk of death due to increased risk of lung transplantation due to increased risk of lung transplantation due to increased risk of death due to increased risk of lung transplantation due to increased risk of lung transplantation due to increased risk of death due to increased risk of lung transplantation due to increased risk of death due to increased risk of lung transplantation due to increased risk of lung transplantation due to increased risk of death due The purpose of this study is to clarify the relationship between the clinical status of lung transplant recipients and the use of extracted lung tissue, to focus attention on the evolution of pulmonary hypertension in recent years, to clarify the molecular expectations of therapeutic targets, and to develop new therapeutic agents for group 3 PH. In the third year of this year, we collected data, analyzed the clinical data, and found that the presence of Group 3 pulmonary hypertension, the future impact of patients in transplant waiting, and the possibility of preparing papers. We also found that the research representative's design changes during the year, and the research difficulties were caused. It is impossible to study the clinical data of the patients before the operation. General morphologic evaluation (HE staining and EVG staining), immunohistochemical evaluation (antibody staining), quantitative evaluation of pulmonary hypertension (tendonized arteries), and quantitative evaluation of lung tissue after lung transplantation were performed.