2001 Fiscal Year Annual Research Report

分子・遺伝子生物学をベースとした肝硬変肝細胞の再生能力活性化に関する研究

Research Project

Project/Area Number	11307022
Research Institution	KYOTO UNIVERSITY
Principal Investigator	山岡義生京都大学, 医学研究科, 教授 (90089102)
Co-Investigator(Kenkyū-buntansha)	山本成尚京都大学, 医学研究科, 助手 (30253298) 山本雄造京都大学, 医学研究科, 講師 (70281730) 嶌原康行京都大学, 医学研究科, 助教授 (30196498)
Keywords	肝再生 / レプチン / 肝硬変 / 伊藤細胞 / 遺伝子導入 / ストレス蛋白 / 細胞外マトリックス / 糖代謝
Research Abstract	前年に引き続き、肝硬変を伴う肝切除症例にて、通常の検査のほかに、術前日・術後2日目・術後21日目の血中レプチン濃度の測定、術前・術後21日目の肝volumemetryを施行した。術後合併症を伴う症例を除外し、解析可能な症例は24例であった。レプチンの肝再生能に対する影響を解析したところ、男性症例(n=18)において、血中レプチン濃度は体脂肪率(R2=0.77)、およびBMI(R2=0.675)と強い相関を認めた。Z1,Z2症例において血中レプチン濃度はZO症例よりも高い傾向をみたが有意差は認めなかった。肝切除後の再生率は肝切除率と相関する傾向を認めたが(R2=0.395)、肝再生率は血中レプチン濃度と全く相関を示さなかった(R2<0.005)。一方、女性症例(n=6)においては、血中レプチン濃度は体脂肪率(R2=0.926)と強い相関を認めた。切除後の再生率は切除率に伴い増加した(R2=0.769)。しかし、肝再生率は術前のレプチン濃度と負の相関を認めた(R2=0.769)。これは女性患者におけるレプチンが肝再生能を抑制する可能性を示唆するものであった。基礎的研究としては、ラット肝硬変モデルにおけるレプチン産生とレプチン受容体(Ob-R)との関連を解析した。血中レプチン濃度は体脂肪量と相関する傾向を認めたが、肝硬変の程度とは相関しなかった。RT.PCRにて肝臓におけるOb-Rの発現を確認した。硬変肝においては正常肝よりもOb-Raの発現は低下していたが、より機能性の高いisoformであるOb-Rbの発現は確認できなかった。また、星細胞の活性化・筋線維芽細胞化が硬変肝の主要因とされているが、我々は肝細胞を星細胞と共培養することによって、肝細胞の増殖が促進することを確認した。これは肝硬変の進行度と肝再生が関連しうることを示唆する所見であった。

Research Products

(18 results)

All Other

All Publications (18 results)

[Publications] Yamamoto Y: "In situ pedicle resection in left trisegmentectomy of the liver combined with resection of the right hepatic vein to an inferior vena caval segment traspositioned from the infra hepatic portion"J.Am.Coll.Surg.. 192(1). 137-141 (2001)
[Publications] Yokata S: "Increased expression of cytosolic chaperonin CCT in human hepatocellular carcinoma"Cell Stress Chaperones. 6(4). 345-350 (2001)
[Publications] Yonezawa K: "Suppression of TNF-alpha production and neutrophil infiltration during ischemia-reperfusion injury of the liver after heat shock preconditioning"J.Hepatol. 35. 619-627 (2001)
[Publications] Uchinami H: "Effect of Heat Shock Preconditioning on NF-kB/1-kB pathway during Ischemia-Reperfusion Injury of the Rat Liver"Am.J.Physiol Gastrointest Liver Physiol. (in press). (2002)
[Publications] Takeda T: "Heat shock restores insulin secretion after injury by nitric oxide by maintaining glucokinase activity in rat islets"Biochem Biophys Res Commun. 284. 20-25 (2001)
[Publications] Yamamoto Y: "Leberresektion bei Lebercirrhose"Chirurg. 72. 784-793 (2001)
[Publications] Okuyama H: "Regulation of cell growth by redox-mediated extraecllular proteolysis of platelet-derived growth factor beta"J.Bio.Chem.. 276(30). 28274-28280 (2001)
[Publications] Minata M: "Postoperative detection of alpha-fetoprotein mRNA in blood as a predictor for metastatic recurrence of hepatocellular carcinoma"J.Gastroenterol Hepatol. 16(4). 445-451 (2001)
[Publications] Oe S: "Continuous intravenous infusion of deleted form of hepatocyte growth factor attenuates hepatic ischemia reperfusion injury in rats"J Hepatol. 34(6). 832-839 (2001)
[Publications] Okabe H: "Genome-wide analysis of gene expression in human hepatocellular carcinoma using cDNA microarray : identification of genes involved in viral carcinogenesis and tumor progression"Cancer Res.. 61(5). 2129-2137 (2001)
[Publications] Yoshida M: "Suppression of proliferative cholangitis by E2F decoy oligonucleotide"J.Surg.Res.. 102(2). 95-101 (2002)
[Publications] Momoi H: "Microsatellite instability and alternative genetic pathway in intrahepatic cholangiocarcinoma"J.Hepatol.. 35(2). 234-244 (2001)
[Publications] Takeyama O: "Effects of prostaglandin E(1) on the efficacy of xenogeneic extracorporeal liver perfusion in a canine model of acute liver failure"Liver Transpla. 7(6). 526-532 (2001)
[Publications] Fujii H: "Contribution of bone marrow to liver generation cells after partial hepatectomy in mice"J.Hepatol. (in press). (2002)
[Publications] Momoi H: "Comprehensive alleotyping of human intrahepatic cholangiocarcinoma"Clin. Cancer Res.. 7(9). 2648-2655 (2001)
[Publications] Uyama N: "Regulation of cultured rat hepatocyte proliferation by stellate cells"J.Hepatol. (in press). (2002)
[Publications] Uesugi T: "Influence of humoral immunoreaction on hepatic nonparenchymal cell in exnoperfused rat livers"J.Surg.Res.. 99(2). 272-281 (2001)
[Publications] Nishitai R: "Influence of estracorporeal porcine liver perfusion nonhuman primates : minimizing hemolysis improves subsequent survival"Liver Transpl.. 7(7). 615-622 (2001)

2001 Fiscal Year Annual Research Report

分子・遺伝子生物学をベースとした肝硬変肝細胞の再生能力活性化に関する研究

Principal Investigator

山岡 義生 京都大学, 医学研究科, 教授 (90089102)

Research Products

[Publications] Yamamoto Y: "In situ pedicle resection in left trisegmentectomy of the liver combined with resection of the right hepatic vein to an inferior vena caval segment traspositioned from the infra hepatic portion"J.Am.Coll.Surg.. 192(1). 137-141 (2001)

[Publications] Yokata S: "Increased expression of cytosolic chaperonin CCT in human hepatocellular carcinoma"Cell Stress Chaperones. 6(4). 345-350 (2001)

[Publications] Yonezawa K: "Suppression of TNF-alpha production and neutrophil infiltration during ischemia-reperfusion injury of the liver after heat shock preconditioning"J.Hepatol. 35. 619-627 (2001)

[Publications] Uchinami H: "Effect of Heat Shock Preconditioning on NF-kB/1-kB pathway during Ischemia-Reperfusion Injury of the Rat Liver"Am.J.Physiol Gastrointest Liver Physiol. (in press). (2002)

[Publications] Takeda T: "Heat shock restores insulin secretion after injury by nitric oxide by maintaining glucokinase activity in rat islets"Biochem Biophys Res Commun. 284. 20-25 (2001)

[Publications] Yamamoto Y: "Leberresektion bei Lebercirrhose"Chirurg. 72. 784-793 (2001)

[Publications] Okuyama H: "Regulation of cell growth by redox-mediated extraecllular proteolysis of platelet-derived growth factor beta"J.Bio.Chem.. 276(30). 28274-28280 (2001)

[Publications] Minata M: "Postoperative detection of alpha-fetoprotein mRNA in blood as a predictor for metastatic recurrence of hepatocellular carcinoma"J.Gastroenterol Hepatol. 16(4). 445-451 (2001)

[Publications] Oe S: "Continuous intravenous infusion of deleted form of hepatocyte growth factor attenuates hepatic ischemia reperfusion injury in rats"J Hepatol. 34(6). 832-839 (2001)

[Publications] Okabe H: "Genome-wide analysis of gene expression in human hepatocellular carcinoma using cDNA microarray : identification of genes involved in viral carcinogenesis and tumor progression"Cancer Res.. 61(5). 2129-2137 (2001)

[Publications] Yoshida M: "Suppression of proliferative cholangitis by E2F decoy oligonucleotide"J.Surg.Res.. 102(2). 95-101 (2002)

[Publications] Momoi H: "Microsatellite instability and alternative genetic pathway in intrahepatic cholangiocarcinoma"J.Hepatol.. 35(2). 234-244 (2001)

[Publications] Takeyama O: "Effects of prostaglandin E(1) on the efficacy of xenogeneic extracorporeal liver perfusion in a canine model of acute liver failure"Liver Transpla. 7(6). 526-532 (2001)

[Publications] Fujii H: "Contribution of bone marrow to liver generation cells after partial hepatectomy in mice"J.Hepatol. (in press). (2002)

[Publications] Momoi H: "Comprehensive alleotyping of human intrahepatic cholangiocarcinoma"Clin. Cancer Res.. 7(9). 2648-2655 (2001)

[Publications] Uyama N: "Regulation of cultured rat hepatocyte proliferation by stellate cells"J.Hepatol. (in press). (2002)

[Publications] Uesugi T: "Influence of humoral immunoreaction on hepatic nonparenchymal cell in exnoperfused rat livers"J.Surg.Res.. 99(2). 272-281 (2001)

[Publications] Nishitai R: "Influence of estracorporeal porcine liver perfusion nonhuman primates : minimizing hemolysis improves subsequent survival"Liver Transpl.. 7(7). 615-622 (2001)

山岡義生京都大学, 医学研究科, 教授 (90089102)