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KAKEN_26860644seika.pdf
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腎筋連関のエピゲノム解析とホルモンを用いた最適治療によるCKD患者の身体能力改善
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ジンキン レンカン ノ エピゲノム カイセキ ト ホルモン オ モチイタ サイテキ チリョウ ニ ヨル CKD カンジャ ノ シンタイ ノウリョク カイゼン
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Jinkin renkan no epigenomu kaiseki to horumon o mochiita saiteki chiryo ni yoru CKD kanja no shintai noryoku kaizen
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Epigenetic analysis for reno-muscular correlation and optimal hormonal treatment for physical decline in patients with chronic kidney disease
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田蒔, 昌憲
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タマキ, マサノリ
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Tamaki, Masanori
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慶應義塾大学・医学部(信濃町)・助教
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Research team head
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科研費研究者番号 : 90528902
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宮下, 和季
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ミヤシタ, カズトシ
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Miyashita, Kazutoshi
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脇野, 修
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ワキノ, シュウ
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Wakino, Shu
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Research team member
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伊藤, 裕
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イトウ, ヒロシ
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Ito, Hiroshi
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2016
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科学研究費補助金研究成果報告書
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2015
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| Abstract |
慢性腎臓病(CKD)では早期から骨格筋変調を伴い身体能力が低下する(腎筋連関)。軽度CKDモデルである5/6腎摘マウスでは, 骨格筋ミトコンドリア減少(マイトペニア)を伴う持久力低下が骨格筋量と筋力の低下に先行した。マイトペニアの一因としてCKD早期から上昇するTNF-αの関与が示唆された。消化管ホルモンであるアシルグレリン投与にて, 5/6腎摘マウスの骨格筋量と筋力は増加し, さらにエピゲノム制御を介したPGC-1α遺伝子発現増加に伴いマイトペニアと持久力を改善した。一方, 代表的な筋肉増強因子であるIGF-1では骨格筋量と筋力を増加したが, マイトペニアは改善せず, 持久力改善は不十分であった。
A physical decline not only led to lowering quality of life, but also raised risk of all-cause mortality. Chronic kidney disease (CKD) impaired physical performance associated with muscle alteration (reno-muscular correlation) since the early stage. 5/6 nephrectomized mice (5/6Nx mice), a mild CKD model, was shown that decrease in exercise endurance associated with decrease in muscular mitochondria (mitopenia) preceded decrease in muscle strength associated with muscle atrophy. TNF-α, a representative inflammatory cytokine which was increased since the early stage of CKD, was supposed as a candidate of mitopenia. Acylated ghrelin treatment, a gastric hormone, not only increased muscle strength and muscle mass, but improved exercise endurance and mitopenia through epigenetic modification of PGC-1α gene in 5/6Nx mice. Meanwhile, IGF-1 treatment, a muscle anabolic factor, hardly improved exercise endurance and did not improve mitopenia, though increased muscle strength and muscle mass.
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研究種目 : 若手研究(B)
研究期間 : 2014～2015
課題番号 : 26860644
研究分野 : 腎臓学・内分泌学
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