本研究では, 閉経後中高齢女性における習慣的な有酸素性運動が動脈伸展性を増大 させる機序に Klotho が果たす役割を明らかにすることを目的とした. 動脈石灰化モ デルラットでは腎臓における膜 Klotho の発現, 閉経後中高齢女性では血漿における
分泌 Klotho 濃度に焦点を当てて以下の検討を行った. ①動脈石灰化モデルラットに
おいては, 長期の自発運動が腎臓の膜 Klotho 発現と動脈 IMT に及ぼす影響を検討し た. 閉経後中高齢女性においては, 有酸素性運動トレーニングが, ②血漿 Klotho 濃度 に及ぼす影響, ③血漿 Klotho 濃度と動脈伸展性に及ぼす影響, そして, ④血漿Klotho 濃度と血管内皮機能および動脈IMTに及ぼす影響を検討した.
その結果, 動脈石灰化モデルラットにおける長期の自発運動は動脈 IMT を減少さ せたが, 腎臓における膜 Klotho 発現は変化させなかった. すなわち, 腎臓における膜
Klotho発現はIMTの減少に関与していない可能性が示唆された. 一方, 閉経後中高齢
女性における血漿Klotho濃度はベースラインの有酸素性運動能力と関連があり, 12週 間の有酸素性運動トレーニングにより増加した. 血漿 Klotho 濃度はベースラインの 動脈伸展性, 血管内皮機能, IMTと関連があった. また, 12週間の有酸素性運動トレー ニングにより動脈伸展性および血管内皮機能は増大したが, IMT は変化しなかった.
さらに, 有酸素性運動トレーニングによる動脈伸展性および血管内皮機能の増大に血
漿Klotho濃度の増加が関与している可能性が示された.
本研究では, 閉経後中高齢女性における習慣的な有酸素性運動が動脈伸展性を増大 させる機序に血漿Klotho濃度の増加が関与する可能性が示された. さらに, 閉経後中 高齢女性における習慣的な有酸素性運動による血漿 Klotho 濃度の増加は血管内皮機
能を向上させ, 動脈伸展性に影響を与える可能性が示唆された.
謝辞
本研究を終えるにあたり, 懇切丁寧なご指導・ご助言を賜りました指導教員である 筑波大学体育系教授 前田清司先生に心より深く感謝の意を表します. 本博士論文の 主査をお引き受け頂き, ご指導・ご助言を賜りました筑波大学医学医療系教授 竹越 一博先生に深く感謝の意を表します. また, 副指導教員および本博士論文の副査をお 引き受け頂き, 貴重なご指導・ご助言を賜りました筑波大学医学医療系教授 正田純 一先生に心より感謝を申し上げます. 筑波大学体育系准教授 麻見直美先生には, 動 物実験に参加する機会を与えて頂き, また, 副査をお引き受け頂き, ご助言を賜りま したこと, 心より深く感謝を申し上げます. さらに, 副指導教員として, 入学当初よ り暖かいご指導・ご助言を賜りました (元筑波大学教授) 鰺坂隆一先生に心より感謝 申し上げます.
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