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KAKEN_23591875seika.pdf
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Download
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:88.2 KB
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:Dec 11, 2014 |
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sRAGEに着目した脳死移植時代のあらたな肝、小腸虚血再灌流障害抑制法の開発
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sRAGE ニ チャクモク シタ ノウシ イショク ジダイ ノ アラタナ カン、ショウチョウ キョケツ サイカンリュウ ショウガイ ヨクセイホウ ノ カイハツ
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sRAGE ni chakumoku shita noshi ishoku jidai no aratana kan, shocho kyoketsu saikanryu shogai yokuseiho no kaihatsu
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Development of a new effective therapy of ischemia reperfusion injury of liver and small intestine.
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篠田, 昌宏
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シノダ, マサヒロ
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Shinoda, Masahiro
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慶應義塾大学・医学部・講師
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Research team head
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科研費研究者番号 : 50286499
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田邉, 稔
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タナベ, ミノル
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Tanabe, Minoru
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慶應義塾大学・医学部・講師(非常勤)
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Research team member
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科研費研究者番号 : 50197513
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高柳, 淳
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タカヤナギ, アツシ
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Takayanagi, Atsushi
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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 : 80245464
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西山, 亮
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ニシヤマ, リョウ
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Nishiyama, Ryo
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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 : 70528322
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2014
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科学研究費補助金研究成果報告書
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2013
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本研究では国内で2010年より急速に増加している脳死ドナーからの臓器活用拡大を目指し、効果的な肝虚血再灌流障害の治療法開発を目指した。各種炎症性疾患で治療標的として注目されている核内タンパクHigh mobility group box-1(以下HMGB1)とその可溶性受容体(sRAGE)に着目し研究・開発を進めた。
sRAGEを産生するアデノウィルスベクターの作製に難渋したが、代わりにHMGB1阻害作用を持つ別のタンパクHMGB1 Aboxを産生するアデノウイルスベクターの作成に成功した。このウイルスベクターをラットの門脈に投与することで、ラット急性肝不全モデルの予後が改善することを示した。
It is clear that the development of an effective therapy, which would serve as a bridge to liver transplantation or regeneration, is needed to reduce the morbidity and mortality associated with ALF. We paid attention to High-mobility group box1(HMGB1) and sRAGE. HMGB1 has recently been identified as an important mediator of various kinds of acute and chronic inflammation and sRAGE is the soluble receptor of HMGB1.
Although it was difficult to make adenovirus vector which encoded amino acids of sRAGE, we suceeded in making adenovirus vector which encoded amino acids of HMGB1 Box-A protein known to act as a competitive inhibitor of HMGB1. Then, the vector was injcected via the portal vein in rats with acute liver failure. Transfected rats showed decreased hepatic enzymes, plasma HMGB1, and histological findings and survival were significantly improved.
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研究種目 : 基盤研究(C)
研究期間 : 2011～2013
課題番号 : 23591875
研究分野 : 医歯薬学
科研費の分科・細目 : 外科系臨床医学・外科学一般
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