Ischemic preconditioning attenuates morphological and biochemical changes in hepatic ischemia/reperfusion in rats.
OBJECTIVE
Ischemic preconditioning (IPC) has been gradually introduced into clinical liver surgery and transplantation in recent years. However, the protective effects of IPC on hepatic warm ischemia/reperfusion (I/R) injury and the potential mechanisms involved are not fully understood. We aimed to evaluate whether the reduction of apoptotic sinusoidal endothelial cells (SECs), induced by IPC, contributes to its protective effect.


METHODS
Male Wistar rats were randomized into three experimental groups: the continuous clamping group underwent 60 min of 70% hepatic ischemia; the IPC group received 10 min ischemia followed by 10 min reperfusion prior to ischemia, and the sham control (sham) underwent a sham operation without ischemia. Hepatocyte and SEC apoptosis, liver necrotic areas and the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), hyaluronic acid, tumor necrosis factor, myeloperoxidase (MPO) and malondialdehyde were determined. Expression of cysteine-aspartic acid protease-3 (caspase-3) in hepatocytes and SECs was also investigated. Furthermore, the hepatic leukocyte infiltration was assessed by intravital fluorescence microscopy.


RESULTS
IPC exhibited a significant alleviation of their postischemic liver function. Serum AST, ALT and tissue MPO were significantly decreased by IPC, and the degree of hepatocyte and SEC apoptosis was significantly inhibited, as shown by the decreased numbers of adherent leukocytes.


CONCLUSIONS
IPC attenuates hepatic I/R injury by the reduction of leukocyte infiltration, the reduction hepatic enzymatic leakage and the depression of apoptotic cells. SECs are more sensitive to apoptosis induced by warm I/R injury compared to hepatocytes.
Key Laboratory of Combined Multiorgan Transplantation, Ministry of Public Health, Division of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Li-Ming
LM
Jin
Yuan-Xing
YX
Liu
Lin
L
Zhou
Hai-Yang
HY
Xie
Xiao-Wen
XW
Feng
Hui
H
Li
Shu-Sen
SS
Zheng
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D017209:Apoptosis; D001219:Aspartate Aminotransferases / Q000097:blood; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D019610:Cytoprotection; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology; D022781:Hepatocytes / Q000378:metabolism / Q000473:pathology; D006820:Hyaluronic Acid / Q000097:blood; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D019194:Ischemic Preconditioning; D015227:Lipid Peroxidation; D008099:Liver / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009336:Necrosis; D020556:Neutrophil Infiltration; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D052096:Warm Ischemia
D015415:Biomarkers; D014409:Tumor Necrosis Factor-alpha; D008315:Malondialdehyde; D006820:Hyaluronic Acid; D009195:Peroxidase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; C505410:Casp3 protein, rat; D053148:Caspase 3