Sirolimus attenuates reduced-size liver ischemia-reperfusion injury but impairs liver regeneration in rats.
BACKGROUND
Evidence has suggested that immunosuppressive drugs impact ischemia-reperfusion injury.


OBJECTIVE
The purpose of the present study was to evaluate the effect of sirolimus on hepatic injury and regeneration in a rat reduced-size liver ischemia-reperfusion model.


METHODS
Using a newly developed rat reduced-size liver ischemia-reperfusion injury model, the effects of sirolimus were evaluated by assessing liver cell apoptosis and aspartate aminotransferase, myeloperoxidase, and malondialdehyde levels. In addition, liver regeneration after sirolimus treatment was evaluated by measuring liver weight resumption and by the histological examination of bromodeoxyuridine and proliferating cell nuclear antigen expression.


RESULTS
Sirolimus significantly decreased liver cell apoptosis as well as tissue myeloperoxidase and malondialdehyde levels, but impaired postischemic liver regeneration. Ischemia-reperfusion-induced elevation of aspartate aminotransferase serum levels was significantly decreased by sirolimus.


CONCLUSIONS
Despite an impairment of postischemic liver proliferation, sirolimus demonstrated beneficial amelioration of ischemia-reperfusion-induced liver injury in a reduced-size liver model in rats.
Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, Zhejiang Province, People's Republic of China.
Yuan-Xing
YX
Liu
Li-Ming
LM
Jin
Lin
L
Zhou
Hai-Yang
HY
Xie
Guo-Ping
GP
Jiang
Hui
H
Chen
Shu-Sen
SS
Zheng
D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D049109:Cell Proliferation / Q000187:drug effects; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000293:injuries*; D008115:Liver Regeneration / Q000187:drug effects*; D008297:Male; D018375:Neutrophil Activation / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000517:prevention & control*; D020123:Sirolimus / Q000009:adverse effects / Q000494:pharmacology*; D013997:Time Factors
D007166:Immunosuppressive Agents; D001219:Aspartate Aminotransferases; D020123:Sirolimus