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Retracted: Rapamycin Attenuates Liver Graft Injury in Cirrhotic Recipient—The Significance of Down‐Regulation of Rho‐ROCK‐VEGF Pathway
Author(s) -
Man K.,
Su M.,
Ng K.T.,
Lo C. M.,
Zhao Y.,
Ho J.W.,
Sun C.K.,
Lee T.K.,
Fan S.T.
Publication year - 2006
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/j.1600-6143.2005.01231.x
Subject(s) - liver transplantation , medicine , transplantation , hepatic stellate cell , sirolimus , liver injury , viaspan , hepatectomy , andrology , surgery , resection
To investigate whether rapamycin could attenuate hepatic I/R injury in a cirrhotic rat liver transplantation model, we applied a rat orthotopic liver transplantation model using 100% or 50% of liver grafts and cirrhotic recipients. Rapamycin was given (0.2 mg/kg, i.v.) at 30 min before graft harvesting in the donor and 24 h before operation, 30 min before total hepatectomy and immediately after reperfusion in the recipient. Rapamycin significantly improved small‐for‐size graft survival from 8.3% (1/12) to 66.7% (8/12) (p = 0.027). It also increased 7‐day survival rates of whole grafts (58.3%[7/12] vs. 83.3%[10/12], p = 0.371). Activation of hepatic stellate cells was mainly found in small‐for‐size grafts during the first 7 days after liver transplantation. Rapamycin suppressed expression of smooth muscle actin, which is a marker of hepatic stellate cell activation, especially in small‐for‐size grafts. Intragraft protein expression and mRNA levels of vascular endothelial growth factor (VEGF) were down‐regulated by rapamycin at 48 h both in whole and small‐for‐size grafts. Consistently, mRNA levels and protein expression of Rho and ROCK I were decreased by rapamycin during the 48 h after liver transplantation. In conclusion, rapamycin attenuated graft injury in a cirrhotic rat liver transplantation model by suppression of hepatic stellate cell activation, related to down‐regulation of Rho‐ROCK‐VEGF pathway.