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KAKEN_24592649seika.pdf
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Title |
Title |
糖尿病網膜症におけるAMPKの役割
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Kana |
トウニョウビョウ モウマクショウ ニ オケル AMPK ノ ヤクワリ
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Romanization |
Tonyobyo momakusho ni okeru AMPK no yakuwari
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Roles of AMP-activated protein kinase in diabetes-induced retinal inflammation.
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持丸, 博史
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モチマル, ヒロシ
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Romanization |
Mochimaru, Hiroshi
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Affiliation |
慶應義塾大学・医学部・助教
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Research team head
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科研費研究者番号 : 90424168
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永井, 紀博
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ナガイ, ノリヒロ
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Romanization |
Nagai, Norihiro
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Affiliation |
慶應義塾大学・医学部・助教
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Research team member
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科研費研究者番号 : 10327611
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小沢, 洋子
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Kana |
オザワ, ヨウコ
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Romanization |
Ozawa, Yoko
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Affiliation |
慶應義塾大学医学部・講師
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Research team member
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科研費研究者番号 : 90265885
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2015
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科学研究費補助金研究成果報告書
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2014
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Abstract |
糖尿病網膜症の病態には炎症が大きく関与し, 抗炎症因子の活性低下が関与する可能性があり, 細胞のエネルギー状態により制御されるAMP activated protein kinase(AMPK)は糖尿病網膜症の病態に関与する可能性がある。申請者らは糖尿病モデルマウスとしてストレプトゾトシン誘導1型モデルマウスを作製し, 網膜組織内のAMPKレベルが低下すること, および糖尿病モデルマウスでは白血球接着が亢進することを見出した。そして, AMPK活性化剤であるレスベラトロールを投与した際の病態予防効果を見あることを見出した。
The streptozotocin-induced diabetes were treated with resveratrol orally at 50 mg/kg for 7 days or with AICAR intraperitoneally at 100 mg/kg 24 hours before death. Induction of diabetes in mice led to retinal AMPK dephosphorylation, which was significantly reversed by either resveratrol or AICAR. Either resveratrol or AICAR significantly reversed SIRT1 deactivation and NF-κB phosphorylation, both of which were induced in the diabetic retina. Administration of resveratrol to diabetic mice significantly reduced diabetes-induced retinal leukocyte adhesion, together with retinal expression of ICAM-1 and VEGF. The present findings reveal that diabetes-induced retinal inflammation stems from downregulation of the AMPK pathway, leading subsequently to SIRT1 deactivation and NF-κB activation. The data also suggest the potential use of the AMPK activator resveratrol as a therapeutic agent for diabetic retinopathy.
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研究種目 : 基盤研究(C)
研究期間 : 2012~2014
課題番号 : 24592649
研究分野 : 眼科
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