Endothelin-1 derived from spleen might modulate hepatic stellate cell and increase intrahepatic resistance in liver cirrhosis.

• Project/Area Number: 21791296
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Digestive surgery
• Research Institution: Kyushu University
• Principal Investigator: KINJO Nao Kyushu University, 大学病院, 特任助教 (00507791)
• Project Period (FY): 2009 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2010: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 門脈圧亢進症 / 肝内微小循環 / 肝硬変症 / エンドセリン-1 / 脾臓 / 肝硬変 / 肝脾相関 / 脾腫 / 肝内抵抗 / エンドセリン

Research Abstract

The aim of study is to elucidate that endothelin-1 derived from spleen might modulate hepatic stellate cell and increase intrahepatic resistance in liver cirrhosis. mRNA of Endothelin- 1 (ET- 1) was significantly more synthesized in the spleen of cirrhotic patients than that of nonportal hypertensive patients. The study using bile duct ligated rats showed that ET- 1 in the portal vein was higher in bile-duct ligated (BDL) rats than in sham operated rats (4.17ア0.62 pg/ml vs 1.81ア0.15 pg/ml, p<0.05). Rho A and Rock II expression in the liver of BDL rats was significantly higher than that of sham operated rats (p<0.05) and splenectomy decreased Rho A and Rock II expression in the liver of BDL rats (p<0.05). Phosphorylation of moesin, which is substrate of Rho kinase, was significantly increased in the BDL rats than sham operated rats (p<0.001), and splenectomy decreased phosphorylation of moesin in the liver of BDL rats (p<0.05). In conclusion, ET-1 derived from spleen might modulate hepatic stellate cell, leading to increase intrahepatic resistance in cirrhotic patients.

Research Products

• [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, Tolnikawa M, Yamashita N, Konishi K, Tanoue K, Shirabe K, Hashizume M, Maehara Y.
  • Journal Title: Br J Surg. 97(6)(910-916) Pages: 910-916
• [Journal Article] Risk factors for portal venous thrombosis after splenectomy in patients with cirrhosis and portal hypertension. (2010)
  • Author(s): Kinio N, Kawanaka H, Akahoshi T, Tomikawa M, Yamashita N, Konishi K, Tanoue K, Shirabe K, Hashizume M, Maehara Y.
  • Journal Title: Br J Surg. 97(9) Pages: 1452-1452
• [Journal Article] Value of Laparoscopic Splenectomy as Salvage Treatment for Relapsed Thrombocytopenia after Partial Splenic Arterial Embolization. (2010)
  • Author(s): Hashimoto N, Akahoshi T, Tomikawa M, Kawanaka H, Konishi K, Uehara H, Kinio N, Korenaga D, Takenaka K, Maehara Y.
  • Journal Title: Dig Surg. 27(6) Pages: 515-520
• [Journal Article] The efficacy of balloon-occluded retrograde transvenous obliteration on small intestinal variceal bleeding. (2010)
  • Author(s): Hashimoto N, Akahoshi T, Yoshida D, Kinio N, Konishi K, Uehara H, Nagao Y, Kawanaka H, Tomikawa M, Maehara Y.
  • Journal Title: Surgery. 148(1) Pages: 145-150
• [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, Akahoshi T, Kinio N, Konishi K, Yoshida D, Anegawa G, Yamaguchi S, Uehara H, Hashimoto N, Tsutsumi N, Tomikawa M, Maehara Y.
  • Journal Title: Ann Surg. 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, Kinio N, Hashimoto N, Ikegami T, Soejima Y, Taketomi A, Maehara Y.
  • Journal Title: Surg Laparosc Endosc Percutan Tech. 19(6) Pages: 484-487
• [Journal Article] Effect of laparoscopic splenectomy on portal hypertensive gastropathy in cirrhotic patients with portal hypertension. (2009)
  • Author(s): Anegawa G, Kawanaka H, Uehara H, Akahoshi T, Konishi K, Yoshida D, Kinjo N, Hashimoto N, Tomikawa M, Hashizume M, Maehara Y.
  • Journal Title: J Gastroenterol Hepatol. 24(9) Pages: 1554-1558
• [Journal Article] Technical standardization of laparoscopic splenectomy harmonized with hand-assisted laparoscopic surgery for patients with liver cirrhosis and hypersplenism. (2009)
  • Author(s): Kawanaka H, Akahoshi T, Kinio N, Konishi K, Yoshida D, Anegawa G, Yamaguchi S, Uehara H, Hashimoto N, Tsutsumi N, Tomikawa M, Koushi K, Harada N, Ikeda Y, Korenaga D, Takenaka K, Maehara Y.
  • Journal Title: J Hepatobiliary Pancreat Surg. 16(6) Pages: 749-757
• [Presentation] 硬変肝において脾臓摘出術が肝微小循環に及ぼす影響についての検討 (2010)
  • Author(s): 上原英雄、赤星朋比古、金城直、橋本直隆、長尾吉泰、家守雅大、富川盛雅、武冨紹信、調憲、前原喜彦
  • Organizer: 第65回日本消化器外科学会
  • Year and Date: 2010-07-15
• [Presentation] 肝硬変/門脈圧充進症に対する腹腔鏡下脾摘術の術中出血量に関する臨床因子の検討 (2010)
  • Author(s): 金城直、赤星朋比古、家守雅大、長尾吉泰、橋本直隆、上原英雄、小西晃造、富川盛雅、調憲、田上和夫、橋爪誠、前原喜彦
  • Organizer: 第110回日本外科学会定期学術集会
  • Place of Presentation: 名古屋(一般口演)
• [Presentation] 慢性C型肝炎/肝硬変患者に対する脾摘後肝機能改善効果に関する検討 (2010)
  • Author(s): 金城直、赤星朋比古、吉武宣明、家守雅大、長尾吉泰、橋本直隆、上原英雄、富川盛雅、橋爪誠、前原喜彦
  • Organizer: 第22回日本肝胆膵外科学会総会
  • Place of Presentation: 仙台
• [Presentation] 要望演題「障害肝合併における脾臓摘出術の功罪」、慢性C型肝炎/肝硬変患者に対する脾摘後肝機能改善効果に関する検討 (2010)
  • Author(s): 金城直、赤星朋比古、吉武宣明、家守雅大、長尾吉泰、橋本直隆、上原英雄、富川盛雅、橋爪誠、前原喜彦
  • Organizer: 第65回日本消化器外科学会定期学術集会
  • Place of Presentation: 下関