Grant-in-Aid for Scientific Research (B)
|Allocation Type||Single-year Grants|
|Research Institution||Kurume University|
TANIKAWA Kyuichi Kurume University School of Medicine, 2nd Department of Medicine, Prof., 医学部, 教授 (10080649)
SAKAMOTO Masaharu Kurume University School of Medicine, 2nd Department of Medicine, Assistant, 医学部, 助手 (60248367)
GONDO Kazuhisa Kurume University School of Medicine, 2nd Department of Medicine, Assistant, 医学部, 助手 (00186909)
TORIMURA Takuji Kurume University School of Medicine, 2nd Department of Medicine, Assistant, 医学部, 助手 (60197986)
UENO Takato Kurume University School of Medicine, 2nd Department of Medicine, Assistant Prof, 医学部, 講師 (70176618)
|Project Period (FY)
1994 – 1996
Completed(Fiscal Year 1996)
|Budget Amount *help
¥6,300,000 (Direct Cost : ¥6,300,000)
Fiscal Year 1996 : ¥900,000 (Direct Cost : ¥900,000)
Fiscal Year 1995 : ¥1,200,000 (Direct Cost : ¥1,200,000)
Fiscal Year 1994 : ¥4,200,000 (Direct Cost : ¥4,200,000)
|Keywords||liver cirrhosis / hepatic sinusoidal microcirculation / hepatic stellate cell (Ito cell) / endothelin-1 / endothelin-1 receptor / alpha-smooth muscle actin / nitric oxide / 神経終末 / エンドセリン-1リセプター / インターロイキン1β / デスミン / アクチン / ミオシン / サブスタンス-P / VIP / エンドセリン-I|
We performed the following studies to understand the changes of hepatic sinusoidal microcirculation in liver cirrhosis.
1. Studies of human normal liver tissues and cirrhotic liver tissues.
Immunolocalization of alpha-smooth muscle actin (alpha-SMA) and endothelin-1 receptor (ET-1R) was significantly increased along the sinusoidal walls in cirrhotic liver compared with normal liver. These products were mainly localized in hepatic stellate cells (HSCs). However, nerve endings and immunolocalization of S-100 protein were markedly decreased in cirrhotic liver compared with normal liver.
2. Studies of hepatic microcirculation using a thioacetamide treated rat cirrhosis model.
The elevation of the portal pressure and the decrease of the portal and hepatic blood flows were induced by the injection of L-NMMA,which is a nitric oxide (NO) inhibitor, in the portal vein.
3. In vitro studies using rat cultured HSCs.
(1) Cultured rat HSCs contracted in response to the addition of ET-1, and relaxd in response to the elevation of intracellular NO with interluikin-1 beta treatment. Moreover, immunofluorescent intensity of anti-cyclic-GMP in HSCs was significantly increased after IL-1 beta addition compared with before IL-1 beta treatment.
(2) Immunofluorescent intensity of anti-alpha-SMA and anti-ET-1R in HSCs obtained from normal liver and cirrhotic liver or rats was examined with a confocal laser-scanning microscope.
Immunofluorescent intensity of these antibodies was significantly increased in HSCs of the cirrhosis group compared with the normal group.
Based on these results, the contraction and relaxation of HSCs through ET-1 and NO rather than through intralobular innervation are suggested to be deeply involved in hepatic sinusoidal microcirculation in liver cirrhosis.