TY - JOUR
T1 - Endothelin-1 derived from spleen-activated Rho-kinase pathway in rats with secondary biliary cirrhosis
AU - Uehara, Hideo
AU - Akahoshi, Tomohiko
AU - Kawanaka, Hirohumi
AU - Hashimoto, Naotaka
AU - Nagao, Yoshihiro
AU - Tomikawa, Morimasa
AU - Taketomi, Akinobu
AU - Shirabe, Ken
AU - Hashizume, Makoto
AU - Maehara, Yoshihiko
N1 - Copyright:
Copyright 2012 Elsevier B.V., All rights reserved.
PY - 2012/10
Y1 - 2012/10
N2 - Aim: Splenectomy or partial splenic embolism has been reported to improve liver function in patients with hypersplenism and liver dysfunction. The aim of this study was to investigate the mechanism of improvement after splenectomy. Methods: Liver cirrhosis was induced by bile duct ligation (BDL). Rats underwent sham operation, splenectomy (Sp group), BDL, or BDL plus splenectomy (BDL+Sp group), and were subjected to experiments at 2weeks after the operation. Portal venous pressure (PVP) and hepatic tissue blood flow (HTBF) were measured in each group. The plasma concentration of endothelin-1 (ET-1) and endothelial nitric oxide synthase (eNOS), RhoA and Rho-kinase expressions were studied. Results: There were significant differences in PVP (17.9±0.91 vs 23.3±3.91cmH 2O; P<0.01) and HTBF (16.6±1.72 vs 13.3±1.82mL/min; P<0.01) between the BDL+Sp and BDL groups. In the liver of BDL rats, eNOS phosphorylation and NOx levels were decreased, accompanied by RhoA activation compared with the BDL+Sp group. Splenectomy decreased serum ET-1 levels, RhoA activation and consequently increased eNOS phosphorylation. Conclusion: ET-1 derived from the spleen might increase intrahepatic resistance by downregulating Rho signaling in liver cirrhosis. Splenectomy for splenomegaly in liver cirrhosis might partially improve liver function by enhancing intrahepatic microcirculation.
AB - Aim: Splenectomy or partial splenic embolism has been reported to improve liver function in patients with hypersplenism and liver dysfunction. The aim of this study was to investigate the mechanism of improvement after splenectomy. Methods: Liver cirrhosis was induced by bile duct ligation (BDL). Rats underwent sham operation, splenectomy (Sp group), BDL, or BDL plus splenectomy (BDL+Sp group), and were subjected to experiments at 2weeks after the operation. Portal venous pressure (PVP) and hepatic tissue blood flow (HTBF) were measured in each group. The plasma concentration of endothelin-1 (ET-1) and endothelial nitric oxide synthase (eNOS), RhoA and Rho-kinase expressions were studied. Results: There were significant differences in PVP (17.9±0.91 vs 23.3±3.91cmH 2O; P<0.01) and HTBF (16.6±1.72 vs 13.3±1.82mL/min; P<0.01) between the BDL+Sp and BDL groups. In the liver of BDL rats, eNOS phosphorylation and NOx levels were decreased, accompanied by RhoA activation compared with the BDL+Sp group. Splenectomy decreased serum ET-1 levels, RhoA activation and consequently increased eNOS phosphorylation. Conclusion: ET-1 derived from the spleen might increase intrahepatic resistance by downregulating Rho signaling in liver cirrhosis. Splenectomy for splenomegaly in liver cirrhosis might partially improve liver function by enhancing intrahepatic microcirculation.
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U2 - 10.1111/j.1872-034X.2012.01021.x
DO - 10.1111/j.1872-034X.2012.01021.x
M3 - Article
C2 - 22594838
AN - SCOPUS:84866772996
VL - 42
SP - 1039
EP - 1047
JO - Hepatology Research
JF - Hepatology Research
SN - 1386-6346
IS - 10
ER -
