Multidisciplinary treatment focusing on impaired intrahepatic microcirculation and splenic dysfunction in liver cirrhosis and portal hypertension

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K10169
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: National Hospital Organization, Beppu Medical Center
• Principal Investigator: Kawanaka Hirofumi 独立行政法人国立病院機構別府医療センター(臨床研究部), 臨床研究部, 臨床研究部長 (10363334)
• Co-Investigator(Kenkyū-buntansha): 赤星 朋比古 九州大学, 医学研究院, 准教授 (20336019) ; 下田 慎治 九州大学, 大学病院, 准教授 (30279319) ; 前原 喜彦 九州大学, 医学研究院, 教授 (80165662)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 脾門脈外科 / 門脈圧亢進症 / 脾機能亢進症 / 類洞内皮細胞 / EndMT / 肝内微小循環障害 / 脾腫

Outline of Final Research Achievements

Portal hypertension with liver cirrhosis is characterized by impaired intrahepatic microcirculation with sinusoidal endothelial cell (SEC) dysfunction and portal hypertensive splenopathy. We herein aimed to investigate whether endothelial-mesenchymal transition (EndMT) is associated with SEC dysfunction; whether increased shear stress in portal circulation by B-RTO affects NO concentration in hepatic vein blood; and whether splenomegaly is related to splenic neovascularization. In cirrhotic models with Tie-2 GFP and Tie-2 LacZ mouse, EndMT was not likely to be associated with SEC dysfunction. Augmented portal shear stress by B-RTO increased NO concentration in hepatic vein blood. Decreased neovascularization by Sorafenib (anti-VEGFR agent) shrank splenic volume and vein. In conclusion, therapeutic strategy focusing on impaired intrahepatic microcirculation and controlling splenic function may provide a feasible multidisciplinary treatment of liver cirrhosis and portal hypertension.

Free Research Field

消化器外科学