Korean J Hepatol.  2011 Jun;17(2):139-147. 10.3350/kjhep.2011.17.2.139.

The effect of preconditioning on liver regeneration after hepatic resection in cirrhotic rats

• Min SO
• Kim SH
• Lee SW
• Cho JA
• Kim KS

• KMID: 1015573
• DOI: http://doi.org/10.3350/kjhep.2011.17.2.139

Abstract

BACKGROUND/AIMS
Ischemic preconditioning (IP) decreases severity of liver necrosis and has anti-apoptotic effects in previous studies using liver regeneration in normal rats. This study assessed the effect of IP on liver regeneration after hepatic resection in cirrhotic rats.
METHODS
To induce liver cirrhosis, thioacetamide (300 mg/kg) was injected intraperitoneally into Sprague-Dawley rats twice per week for 16 weeks. Animals were divided into four groups: non-clamping (NC), total clamping (TC), IP, and intermittent clamping (IC). Ischemic injury was induced by clamping the left portal pedicle including the portal vein and hepatic artery. Liver enzymes alanine transaminase (ALT) and aspartate aminotransferase (AST) were measured to assess liver damage. Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) staining for apoptosis and proliferating cell nuclear antigen (PCNA) staining for cell replication were also performed.
RESULTS
Day-1 ALT and AST were highest in IP, however, levels in NC and IC were comparably low on days 1-7. There was no significant correlation of AST or ALT with experimental groups (P=0.615 and P=0.186). On TUNEL, numbers of apoptotic cells at 100x magnification (cells/field) were 31.8+/-24.2 in NC, 69.0+/-72.3 in TC, 80.2+/-63.1 in IP, and 21.2+/-20.8 in IC (P<0.05). When regeneration capacity was assessed by PCNA staining, PCNA-positive cells (cells/field) at 400x were 3.4+/-6.0 in NC, 16.9+/-69 in TC, 17.0+/-7.8 in IP and 7.4+/-7.6 in IC (P<0.05).
CONCLUSIONS
Although regeneration capacity in IP is higher than IC, the liver is vulnerable to ischemic damage in cirrhotic rats. Careful consideration is needed in applying IP in the clinical setting.

Keyword

Liver cirrhosis; Ischemic preconditioning; Liver regeneration; Hepatectomy; Apoptosis

MeSH Terms

Alanine Transaminase/blood
Animals
Apoptosis
Aspartate Aminotransferases/blood
Constriction
Hepatectomy/methods
Hepatic Artery
*Ischemic Preconditioning
Liver/blood supply
Liver Cirrhosis, Experimental/chemically induced/complications/*pathology
*Liver Regeneration
Proliferating Cell Nuclear Antigen/metabolism
Rats
Rats, Sprague-Dawley
Reperfusion Injury/complications/enzymology/pathology
Thioacetamide/toxicity