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The development of new treatment for improvement of microcirculation in cirrhotic liver

Research Project

Project/Area Number 21591755
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Digestive surgery
Research InstitutionKyushu University

Principal Investigator

AKAHOSHI Tomohiko  九州大学, 医学研究院, 講師 (20336019)

Co-Investigator(Kenkyū-buntansha) MAEHARA Yoshihiko  九州大学, 医学研究院, 教授 (80165662)
TOMIKAWA Morimasa  九州大学, 大学病院, 准教授 (60325454)
MURATA Masaharu  九州大学, 医学研究院, 准教授 (30304744)
Project Period (FY) 2009 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2011: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2010: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2009: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywords肝硬変 / 肝微小循環 / Rho kinase, eNOS / ET-1 / Nitric oxide (NO / ナノカプセル / rho-kinase / VEGF / 脾臓 / 門脈圧亢進症 / Rho kinase阻害剤 / Shear response factor
Research Abstract

Study 1. RhoA and Rho kinase expressions were significantly over expressed in cirrhotic liver accompanied with decrease in eNOS activity. Splenectomy significantly reduce portal vein pressure and improved disturbance of microcirculation in the cirrotic liver. In the liver of cirrhotic rat, Splenectomy also decreased serum ET-1 levels. The ET-1 level was strongly related RhoA activation, and decrease of eNOS phosphorylation. ET-1 derived from the spleen increase intrahepatic resistance by down-regulating Rho signaling in liver cirrhosis.
Study 2. Splenectomy induced thrombocytosis, and increased serotonin content in cirrhotic liver. Stimulation of liver regeneration was indicated by the following parameters : hepatocyte ratio to the entire liver area, Ki67-positive hepatocyte count, and expression of phosphorylated extracellular
signal-regulated kinases. This enhancement of liver regenerationwas negated by ketanserin. Our results showed that splenectomy promoted liver regeneration by increasing serotonin content in liver even under cirrhotic conditions.

Report

(4 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • 2009 Annual Research Report
  • Research Products

    (51 results)

All 2012 2011 2010 2009 2008

All Journal Article (33 results) (of which Peer Reviewed: 21 results) Presentation (17 results) Book (1 results)

  • [Journal Article] Impact of balloon-occluded retrograde transvenous obliteration on management of isolated fundal gastric variceal bleeding2012

    • Author(s)
      Akahoshi T, Tomikawa M, Kamori M, Tsutsumi N, Nagao Y, Hashizume M, Maehara Y.
    • Journal Title

      Hepatol Res

      Volume: 42 Issue: 4 Pages: 385-393

    • DOI

      10.1111/j.1872-034x.2011.00939.x

    • NAID

      10031144251

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Impact of balloon-occluded retrograde transvenous obliteration on management of isolated fundal gastric variceal bleeding2011

    • Author(s)
      Akahoshi T, Tomikawa M, Kamori M, Tsutsumi N, Nagao Y, Hashizume M, Maehara Y
    • Journal Title

      Hepatol Res

      Volume: 19

    • NAID

      10031144251

    • Related Report
      2011 Final Research Report
  • [Journal Article] Roles of vascular endothelial growth factor and endothelial nitric oxide synthase during revascularization and regeneration after partial hepatectomy in a rat model2011

    • Author(s)
      Yoshida D, Akahoshi T, Kawanaka H, Yamaguchi S, Kinjo N, Taketomi A, Tomikawa M, Shirabe K, Maehara Y, Hashizume M
    • Journal Title

      Surg Today

      Volume: 41(12) Pages: 1622-9

    • NAID

      10030229785

    • Related Report
      2011 Final Research Report
  • [Journal Article] Predictive factors for platelet count after laparoscopic splenectomy in cirrhotic patients2011

    • Author(s)
      Yoshida D, Nagao Y, Tomikawa M, Kawanaka H, Akahoshi T, Kinjo N, Uehara H, Hashimoto N, Hashizume M, Maehara Y
    • Journal Title

      Hepatol Int

      Volume: 30

    • Related Report
      2011 Final Research Report
  • [Journal Article] Laparoscopic splenectomy with IFN therapy in one hundred HCV-cirrhotic patients with hypersplenism and thrombocytopenia2011

    • Author(s)
      Akahoshi T, Tomikawa M, Kawanaka H, Furusyo N, Kinjo N, Tsutsumi N, Nagao Y, Hayashi J, Hashizume M, Maehara Y
    • Journal Title

      J Gastroenterol Hepatol

      Volume: 28

    • Related Report
      2011 Final Research Report
  • [Journal Article] Liver regeneration is promoted by increasing serotonin content in rat liver with secondary biliary cirrhosis2011

    • Author(s)
      Nagao Y, Akahoshi T, Kamori M, Uehara H, Hashimoto N, Kinjo N, Shirabe K, Taketomi A, Tomikawa M, Hashizume M, Maehara Y
    • Journal Title

      Hepatol Res

      Volume: 41(8) Pages: 784-94

    • NAID

      10031144151

    • Related Report
      2011 Final Research Report
  • [Journal Article] Modulation of CD4^+ T cell responses following splenectomy in hepatitis C virus-related liver cirrhosis2011

    • Author(s)
      12. Hashimoto N, Shimoda S, Kawanaka H, Tsuneyama K, Uehara H, Akahoshi T, Kinjo N, Taketomi A, Shirabe K, Akashi K, Lleo A, Ansari AA, Gershwin ME, Maehara Y
    • Journal Title

      ClinExpImmunol

      Volume: 165(2) Pages: 243-50

    • Related Report
      2011 Final Research Report
  • [Journal Article] Roles of vascular endothelial growth factor and endothelial nitric oxide synthase during revascularization and regeneration after partial hepatectomy in a rat model2011

    • Author(s)
      Yoshida D., et al
    • Journal Title

      Surg Today

      Volume: 41 Issue: 12 Pages: 1622-9

    • DOI

      10.1007/s00595-010-4484-9

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Predictive factors for platelet count after laparoscopic splenectomy in cirrhotic patients2011

    • Author(s)
      Yoshida D, Akahoshi T, et al
    • Journal Title

      Hepatol Int

      Volume: (Epub ahead of print) Issue: 3 Pages: 657-661

    • DOI

      10.1007/s12072-011-9315-6

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Laparoscopic splenectomy with interferon therapy in 100 hepatitis-C-virus-cirrhotic patients with hypersplenism and thrombocytopenia2011

    • Author(s)
      Akahoshi T, et al
    • Journal Title

      Hepatol Int

      Volume: 27 Issue: 2 Pages: 286-290

    • DOI

      10.1111/j.1440-1746.2011.06870.x

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Successful treatment for hepatic encephalopathy aggravated by portal vein thrombosis with balloonocculuded retrograde transvenous obliteration2011

    • Author(s)
      Hashimoto N., et al
    • Journal Title

      Case Rep Gastroenterol

      Volume: 5 Issue: 2 Pages: 366-71

    • DOI

      10.1159/000330287

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Prediction of improved liver function after balloon-occluded retrograde transvenous obliteration : relation to hepatic vein pressure gradient2011

    • Author(s)
      Uehara H, Akahoshi T, et al
    • Journal Title

      J Gastroenterol Hepatol

      Volume: 27 Issue: 1 Pages: 137-41

    • DOI

      10.1111/j.1440-1746.2011.06835.x

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Liver regeneration is promoted by increasing serotonin content in rat liver with secondary biliary cirrhosis2011

    • Author(s)
      Nagao Y, Akahoshi T, Tomikawa M, Hashizume M, Maehara Y.
    • Journal Title

      Hepatol Res

      Volume: 41 Issue: 8 Pages: 784-794

    • DOI

      10.1111/j.1872-034x.2011.00828.x

    • NAID

      10031144151

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Trends in the treatment outcomes for advanced colorectal cancer : an analysis at a single community hospital in Japan2011

    • Author(s)
      Tomikawa M., et al
    • Journal Title

      Surg Today

      Volume: 41 Issue: 6 Pages: 801-5

    • DOI

      10.1007/s00595-010-4348-3

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Modulation of CD4(+) T cell responses following splenectomy in hepatitis C virus-related liver cirrhosis2011

    • Author(s)
      Hashimoto N., et al
    • Journal Title

      Clin Exp Immunol

      Volume: 165 Issue: 2 Pages: 243-50

    • DOI

      10.1111/j.1365-2249.2011.04393.x

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The efficacy of balloon-occluded retrograde transvenous obliteration on small intestinal variceal bleeding2010

    • Author(s)
      Hashimoto N, Akahoshi T, Yoshida D, Kinjo N, Konishi K, Uehara H, Nagao Y, Kawanaka H, Tomikawa M, Maehara Y.
    • Journal Title

      Surgery

      Volume: 148(1) Pages: 145-50

    • Related Report
      2011 Final Research Report
  • [Journal Article] Risk factors for portal venous thrombosis after splenectomy in patients with cirrhosis and portal hypertension2010

    • Author(s)
      Kinjo N, Kawanaka H, Akahoshi T, Tomikawa M, Yamashita N, Konishi K, Tanoue K, Shirabe K, Hashizume M, Maehara Y.
    • Journal Title

      Br J Surg

      Volume: 97(6) Pages: 910-6

    • Related Report
      2011 Final Research Report
  • [Journal Article] Laparoscopic splenectomy may be a superior supportive intervention for cirrhotic patients with hypersplenism2010

    • Author(s)
      Tomikawa M, Akahoshi T, Sugimachi K, Ikeda Y, Yoshida K, Tanabe Y, Kawanaka H, Takenaka K, Hashizume M, Maehara Y. J
    • Journal Title

      Gastroenterol Hepatol

      Volume: 25(2) Pages: 397-402

    • Related Report
      2011 Final Research Report
  • [Journal Article] Impact of antithrombin III concentrates on portal vein thrombosis after splenectomy in patients with liver cirrhosis and hypersplenism2010

    • Author(s)
      6. Kawanaka H, Akahoshi T, Kinjo N, Konishi K, Yoshida D, Anegawa G, Yamaguchi S, Uehara H, Hashimoto N, Tsutsumi N, Tomikawa M, Maehara Y
    • Journal Title

      Ann Surg

      Volume: 251(1) Pages: 76-83

    • Related Report
      2011 Final Research Report
  • [Journal Article] Electromagnetic thermoablation to treat thrombocytopenia in cirrhotic and hypersplenic rats.2010

    • Author(s)
      Akahoshi T, et al.
    • Journal Title

      J Gastroenterol Hepatol.

      Volume: 25 Pages: 1470-2

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] An assessment of surgery for portal hypertensive patients performed at a single community hospital.2010

    • Author(s)
      Tomikawa M, et al.
    • Journal Title

      Surg Today.

      Volume: 40 Pages: 620-5

    • NAID

      10027396544

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Real-time 3-dimensional virtual reality navigation system with open MRI for breast-conserving surgery.2010

    • Author(s)
      Tomikawa M, et al.
    • Journal Title

      J Am Coll Surg.

      Volume: 210 Pages: 927-33

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Risk factors for portal venous thrombosis after splenectomy in patients with cirrhosis and portal hypertension.2010

    • Author(s)
      Kinjo N, et al.
    • Journal Title

      Br J Surg.

      Volume: 97 Pages: 910-6

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The feasibility and effectiveness of a hand-assisted laparoscopic splenectomy for hypersplenism in patients after living-donor liver transplantation.2010

    • Author(s)
      Uehara H, et al.
    • Journal Title

      Surg Laparosc Endosc Percutan Tech.

      Volume: 19 Pages: 484-7

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The efficacy of balloon-occluded retrograde transvenous obliteration on small intestinal variceal bleeding.2010

    • Author(s)
      Hashimoto N, et al.
    • Journal Title

      Surgery.

      Volume: 148 Pages: 145-50

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effect of thrombopoietin on platelet counts and liver regeneration after partial hepatectomy in a rat model.2010

    • Author(s)
      Shimabukuro R, et al.
    • Journal Title

      Surg Today.

      Volume: 39 Pages: 1054-9

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Laparoscopic splenectomy may be a superior supportive intervention for cirrhotic patients with hypersplenism.2010

    • Author(s)
      Tomikawa M, et al.
    • Journal Title

      J Gastroenterol Hepatol.

      Volume: 25 Pages: 397-402

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Impact of antithrombin III concentrates on portal vein thrombosis after splenectomy in patients with liver cirrhosis and hypersplenism.2010

    • Author(s)
      Kawanaka H, et al.
    • Journal Title

      Ann Surg.

      Volume: 251 Pages: 76-83

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Laparoscopic splenectomy with peginterferon and ribavirin therapy for patients with hepatitis C virus cirrhosis and hypersplenism.2010

    • Author(s)
      Akahoshi T, et al.
    • Journal Title

      Surg Endosc.

      Volume: 24 Pages: 680-5

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effect of laparoscopic splenectomy on portal hypertensive gastropathy in cirrhotic patients with portal hypertension.2010

    • Author(s)
      Anegawa G, et al.
    • Journal Title

      J Gastroenterol Hepatol.

      Volume: 24 Pages: 1554-8

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The feasibility and effectiveness of a hand-assisted laparoscopic splenectomy for hypersplenism in patients after living-donor liver transplantation2009

    • Author(s)
      Uehara H, Kawanaka H, Akahoshi T, Tomikawa M, Kinjo N, Hashimoto N, Ikegami T, Soejima Y, Taketomi A, Maehara Y
    • Journal Title

      Surg Laparosc Endosc Percutan Tech

      Volume: 19(6) Pages: 484-7

    • Related Report
      2011 Final Research Report
  • [Journal Article] Effect of thrombopoietin on platelet counts and liver regeneration after partial hepatectomy in a rat model2009

    • Author(s)
      Shimabukuro R, Kawanaka H, Tomikawa M, Akahoshi T, Konishi K, Yoshida D, Anegawa G, Uehara H, Hashimoto N, Hashizume M, Maehara Y.
    • Journal Title

      Surg Today

      Volume: 39(12) Pages: 1054-9

    • NAID

      10027393206

    • Related Report
      2011 Final Research Report
  • [Journal Article] Effect of thrombopoietin on platelet counts and liver regeneration after partial hepatectomy in a rat model2009

    • Author(s)
      島袋林春, 川中博文, 赤星朋比古, 他
    • Journal Title

      Surgery Today 39

      Pages: 1054-1059

    • NAID

      10027393206

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Presentation] 検体保存センターの登録と解析について2012

    • Author(s)
      赤星朋比古、橋爪誠
    • Organizer
      厚生省特定疾患門脈血行異常症調査研究班平成23年度研究報告書
    • Related Report
      2011 Final Research Report
  • [Presentation] 当科における食道静脈瘤の治療の変遷と成績2011

    • Author(s)
      赤星朋比古
    • Organizer
      第18回日本門脈圧亢進症学会総会
    • Place of Presentation
      福岡
    • Year and Date
      2011-09-15
    • Related Report
      2011 Annual Research Report
  • [Presentation] 食道胃静脈瘤出血に対する治療戦略2011

    • Author(s)
      赤星朋比古
    • Organizer
      第18回日本門脈圧亢進症学会総会
    • Place of Presentation
      福岡
    • Year and Date
      2011-09-15
    • Related Report
      2011 Annual Research Report
  • [Presentation] 腹腔鏡下脾臓摘出術のlatest modern technique2011

    • Author(s)
      赤星朋比古
    • Organizer
      第21回九州内視鏡下外科研究会
    • Place of Presentation
      福岡
    • Year and Date
      2011-09-04
    • Related Report
      2011 Annual Research Report
  • [Presentation] Laparoscopic splenectomy in one hundred HCV-cirrhosis patients with hypersplenisum and thrombocytopenia2011

    • Author(s)
      赤星朋比古
    • Organizer
      International Surgical Week, 2011
    • Place of Presentation
      横浜
    • Year and Date
      2011-08-30
    • Related Report
      2011 Annual Research Report
  • [Presentation] 当科における食道胃静脈瘤における治療の変遷と成績2011

    • Author(s)
      赤星朋比古
    • Organizer
      第81回日本消化器内視鏡学会総会
    • Place of Presentation
      名古屋
    • Year and Date
      2011-08-18
    • Related Report
      2011 Annual Research Report
  • [Presentation] 難治性静脈瘤に対する腹腔鏡下Hassab手術2011

    • Author(s)
      赤星朋比古
    • Organizer
      第47回日本腹部救急医学会総会
    • Place of Presentation
      福岡
    • Year and Date
      2011-08-12
    • Related Report
      2011 Annual Research Report
  • [Presentation] 難治性消化管静脈瘤に対する外科治療の意義2011

    • Author(s)
      赤星朋比古, 他
    • Organizer
      第46回日本腹部救急医学会総会
    • Place of Presentation
      富山
    • Year and Date
      2011-03-18
    • Related Report
      2010 Annual Research Report
  • [Presentation] 食道胃静脈瘤出血に対する当院における救急体制2010

    • Author(s)
      赤星朋比古, 他
    • Organizer
      第38回日本救急医学会総会
    • Place of Presentation
      東京
    • Year and Date
      2010-10-10
    • Related Report
      2010 Annual Research Report
  • [Presentation] 当科における食道静脈瘤に対する治療戦略と成績2010

    • Author(s)
      赤星朋比古, 他
    • Organizer
      第17回日本門脈圧亢進症学会総会
    • Place of Presentation
      富山
    • Year and Date
      2010-09-09
    • Related Report
      2010 Annual Research Report
  • [Presentation] パネルディスカッション「肝硬変合併脾機能亢進症に対する腹腔鏡下脾臓摘出術と合併症についての検討」2010

    • Author(s)
      赤星朋比古、富川盛雅、家守雅大、長尾吉泰、前原喜彦
    • Organizer
      第65回日本消化器外科学会
    • Year and Date
      2010-07-16
    • Related Report
      2011 Final Research Report
  • [Presentation] 肝硬変合併脾機能亢進症に対する腹腔鏡下脾臓摘出術と合併症についての検討2010

    • Author(s)
      赤星朋比古, 他
    • Organizer
      第65回日本消化器外科学会
    • Place of Presentation
      下関
    • Year and Date
      2010-07-16
    • Related Report
      2010 Annual Research Report
  • [Presentation] 腹腔鏡手術に有用なOpen MRIを用いたリアルタイムナビゲーションシステムの開発2010

    • Author(s)
      赤星朋比古, 他
    • Organizer
      第110回日本外科学会
    • Place of Presentation
      東京
    • Year and Date
      2010-04-09
    • Related Report
      2010 Annual Research Report
  • [Presentation] 肝癌合併食道・胃静脈瘤に対する治療戦略2010

    • Author(s)
      赤星朋比古, 他
    • Organizer
      第18回日本消化器関連学会週間(JDDW2010)
    • Place of Presentation
      横浜
    • Related Report
      2010 Annual Research Report
  • [Presentation] 肝硬変における肝内微少循環異常における分子機序の解明2009

    • Author(s)
      赤星朋比古
    • Organizer
      日本門脈圧亢進症学会
    • Place of Presentation
      ホテルハマツ(福島県)
    • Year and Date
      2009-09-10
    • Related Report
      2009 Annual Research Report
  • [Presentation] ワークショップ「肝硬変症における腹腔鏡下脾摘術の臨床的意義についての検討」2009

    • Author(s)
      1.赤星朋比古、富川盛雅、金城直、上原英雄、橋本直隆、長尾吉泰、前原喜彦
    • Organizer
      第64回日本消化器外科学会
    • Year and Date
      2009-07-18
    • Related Report
      2011 Final Research Report
  • [Presentation] 門脈圧亢進症胃粘膜における門脈血行異常症の分子生物学的検討2008

    • Author(s)
      赤星朋比古、前原喜彦
    • Organizer
      厚生省特定疾患門脈血行異常症調査研究班平成20年度研究報告書
    • Related Report
      2011 Final Research Report
  • [Book] (腹腔鏡下)脾蔵摘出術:安全確実な手術を行うための工夫 手術2009

    • Author(s)
      赤星朋比古、川中博文、金城直、小西晃造、富川盛雅、前原喜彦
    • Related Report
      2011 Final Research Report

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Published: 2009-04-01   Modified: 2016-04-21  

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