2003 Fiscal Year Annual Research Report

類洞壁細胞の活性化制御による硬変肝手術侵襲抑制に関する研究-肝切除手術の限界打破に向けて-

Research Project

Project/Area Number	14370388
Research Institution	KYOTO UNIVERSITY
Principal Investigator	長谷川傑京都大学, 医学研究科, 助手 (10362500)
Co-Investigator(Kenkyū-buntansha)	山本雄造秋田大学, 医学部, 教授 (70281730) 波多野悦朗京都大学, 医学研究科, 助手 (80359801)
Keywords	肝切除 / 肝硬変 / 虚血再灌流障害 / 肝類洞壁細胞 / 肝類洞血流 / 分子シャペロン
Research Abstract	ROCK/Rho kinase阻害剤Y-27632前投与による硬変肝虚血再灌流障害抑制効果の検討においては、前年度の研究にて確立しえたチオアセタミド(TAA)投与によるラット肝硬変モデルを用いた生体蛍光顕微鏡による肝微小循環動態の評価を試みたが、硬変肝の表面の凹凸が激しく現状の生体蛍光顕微鏡による適当な評価が困難であった。これを生体蛍光顕微鏡で評価するためには更なる工夫を要すると考えられたため、生体蛍光顕微鏡で評価可能な肝硬変モデルを作成するために薬剤投与方法の変更などを追加試行中である。一方、LPS投与によるendotoxin shockモデルにおける肝障害抑制効果についての検討では、Y-27632前投与により肝微小循環動態および肝障害が抑制された。さらに、HO-1肝特異的誘導効果を持つpyrrolidine dithiocarbamate前投与による肝虚血再灌流障害抑制効果の検討においては、まず正常肝について検討したところ、CO分子発生量増加により肝類洞の著明な拡張が得られ、結果的に肝微小循環動態および肝障害が有意に抑制されることが証明された。これは肝類洞の拡張により血流抵抗が減じる効果のみならず、類洞内皮における接着分子等のinteractionによりもたらされる循環障害の軽減効果をも合わせもつものであろう事を示唆する。肝硬変における類洞灌流の障害を改善するための新たな戦略を開発する基礎となりうるであろうと考えている。

Research Products

(12 results)

All Other

All Publications (12 results)

[Publications] Hata K: "Induction of heme oxygenase-1 and dilataion of hepatic sinusoids by an administration of pyrrolidine dithiocarbamate in rat livers"J Surg Res.. 115(2). 310-317 (2003)
[Publications] Uyama N: "Carbenoxolone inhibits DNA synthesis and collagen gene expression in rat hepatic stellate cells in culture"J Hepatol.. 39(5). 749-755 (2003)
[Publications] Harada N: "Inactivation of the small GTPase Rac1 protects the liver from ischemia/reperfusion injury in the rat"Surgery. 134(3). 480-491 (2003)
[Publications] Fujikawa T: "purification of adult hepatic progenitor cells using green fluorescent protein (GFP-transgenic mice and fluorescence-activated cell sorting"J Hepatol.. 39(2). 162-170 (2003)
[Publications] Nitta T: "Myoglobin gene expression attenuates hepatic ischemia reperfusion injury"J Surg Res.. 110(2). 322-331 (2003)
[Publications] Azuma H: "Enrichment of hepatic progenitor cells from adult mouse liver"Hepatology. 37(6). 1385-1394 (2003)
[Publications] Okuyama H: "Overexpression of thioredoxin prevents acute hepatitis caused by thioacetamide or lipopolysaccharide in mice"Hepatology. 37(5). 1015-1025 (2003)
[Publications] Yamagami K: "Heat-shock preconditioning protects fatty livers in genetically obese Zucker rats from microvascular perfusion failure after ischemia reperfusion"Tranpl Int.. 16(8). 456-463 (2003)
[Publications] Nishio T: "Increased expression of collagenase in the liver induces hepatocyte proliferation with cytoplasmic accumulation of beta-catenin in the rat"J Hepatol.. 38(4). 468-475 (2003)
[Publications] Ikeda F: "Reduction of hepatic ischemia/reperfusion-induced injury by a specific ROCK/Rho kinase inhibitor Y-27632"J Surg Res.. 109(2). 155-160 (2003)
[Publications] Oe S: "A trial on regeneration therapy of rat liver cirrhosis by controlled release of hepatocyte growth factor"J Control Release. 7;88(2). 193-200 (2003)
[Publications] Iimuro Y: "Delivery of matrix metalloproteinase-1 attenuates established liver fibrosis in the rat"Gastroenterology. 124(2). 445-458 (2003)

2003 Fiscal Year Annual Research Report

類洞壁細胞の活性化制御による硬変肝手術侵襲抑制に関する研究-肝切除手術の限界打破に向けて-

Principal Investigator

長谷川 傑 京都大学, 医学研究科, 助手 (10362500)

Research Products

[Publications] Hata K: "Induction of heme oxygenase-1 and dilataion of hepatic sinusoids by an administration of pyrrolidine dithiocarbamate in rat livers"J Surg Res.. 115(2). 310-317 (2003)

[Publications] Uyama N: "Carbenoxolone inhibits DNA synthesis and collagen gene expression in rat hepatic stellate cells in culture"J Hepatol.. 39(5). 749-755 (2003)

[Publications] Harada N: "Inactivation of the small GTPase Rac1 protects the liver from ischemia/reperfusion injury in the rat"Surgery. 134(3). 480-491 (2003)

[Publications] Fujikawa T: "purification of adult hepatic progenitor cells using green fluorescent protein (GFP-transgenic mice and fluorescence-activated cell sorting"J Hepatol.. 39(2). 162-170 (2003)

[Publications] Nitta T: "Myoglobin gene expression attenuates hepatic ischemia reperfusion injury"J Surg Res.. 110(2). 322-331 (2003)

[Publications] Azuma H: "Enrichment of hepatic progenitor cells from adult mouse liver"Hepatology. 37(6). 1385-1394 (2003)

[Publications] Okuyama H: "Overexpression of thioredoxin prevents acute hepatitis caused by thioacetamide or lipopolysaccharide in mice"Hepatology. 37(5). 1015-1025 (2003)

[Publications] Yamagami K: "Heat-shock preconditioning protects fatty livers in genetically obese Zucker rats from microvascular perfusion failure after ischemia reperfusion"Tranpl Int.. 16(8). 456-463 (2003)

[Publications] Nishio T: "Increased expression of collagenase in the liver induces hepatocyte proliferation with cytoplasmic accumulation of beta-catenin in the rat"J Hepatol.. 38(4). 468-475 (2003)

[Publications] Ikeda F: "Reduction of hepatic ischemia/reperfusion-induced injury by a specific ROCK/Rho kinase inhibitor Y-27632"J Surg Res.. 109(2). 155-160 (2003)

[Publications] Oe S: "A trial on regeneration therapy of rat liver cirrhosis by controlled release of hepatocyte growth factor"J Control Release. 7;88(2). 193-200 (2003)

[Publications] Iimuro Y: "Delivery of matrix metalloproteinase-1 attenuates established liver fibrosis in the rat"Gastroenterology. 124(2). 445-458 (2003)

長谷川傑京都大学, 医学研究科, 助手 (10362500)