| Project/Area Number |
15K10169
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Digestive surgery
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| Research Institution | National Hospital Organization, Beppu Medical Center |
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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)
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| 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)
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2015: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
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| 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 / EndMt / 脾硬度 |
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| 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.
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