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

2011 Fiscal Year Final Research Report

• Project/Area Number: 21591755
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Kyushu 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
• Keywords: 肝硬変 / 肝微小循環 / Rho kinase, eNOS

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.

Research Products

• [Journal Article] Impact of balloon-occluded retrograde transvenous obliteration on management of isolated fundal gastric variceal bleeding (2011)
  • Author(s): Akahoshi T, Tomikawa M, Kamori M, Tsutsumi N, Nagao Y, Hashizume M, Maehara Y
  • Journal Title: Hepatol Res Volume: 19
• [Journal Article] Roles of vascular endothelial growth factor and endothelial nitric oxide synthase during revascularization and regeneration after partial hepatectomy in a rat model (2011)
  • 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
• [Journal Article] Predictive factors for platelet count after laparoscopic splenectomy in cirrhotic patients (2011)
  • 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
• [Journal Article] Laparoscopic splenectomy with IFN therapy in one hundred HCV-cirrhotic patients with hypersplenism and thrombocytopenia (2011)
  • 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
• [Journal Article] Liver regeneration is promoted by increasing serotonin content in rat liver with secondary biliary cirrhosis (2011)
  • 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
• [Journal Article] Modulation of CD4^+ T cell responses following splenectomy in hepatitis C virus-related liver cirrhosis (2011)
  • 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
• [Journal Article] The efficacy of balloon-occluded retrograde transvenous obliteration on small intestinal variceal bleeding (2010)
  • 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
• [Journal Article] Risk factors for portal venous thrombosis after splenectomy in patients with cirrhosis and portal hypertension (2010)
  • 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
• [Journal Article] Laparoscopic splenectomy may be a superior supportive intervention for cirrhotic patients with hypersplenism (2010)
  • 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
• [Journal Article] Impact of antithrombin III concentrates on portal vein thrombosis after splenectomy in patients with liver cirrhosis and hypersplenism (2010)
  • 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
• [Journal Article] The feasibility and effectiveness of a hand-assisted laparoscopic splenectomy for hypersplenism in patients after living-donor liver transplantation (2009)
  • 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
• [Journal Article] Effect of thrombopoietin on platelet counts and liver regeneration after partial hepatectomy in a rat model (2009)
  • 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
• [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
  • Year and Date: 20120000
• [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
• [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
• [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
  • Year and Date: 20080000
• [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
  • Total Pages: 1153-1160