Effect of Ischemic Preconditioning and Postconditioning on Liver Regeneration in Prepubertal Rats

Abstract

BackgroundLiver regeneration has great importance for transplantation, especially in children; however, it has not been studied sufficiently in development animals. Ischemia-reperfusion injury is a problem, and strategies such as ischemic preconditioning and postconditioning are not well defined regarding regeneration. ObjectiveThis study sought to evaluate liver regeneration with modulation by ischemic preconditioning and postconditioning in prepubertal rats subjected to total ischemia and reperfusion. MethodsThirty-five 5-week-old female Wistar rats were divided into groups of 7 animals each: control group (SHAM), 70% hepatectomy (HEP), total ischemia 30 minutes before hepatectomy (IR), ischemic preconditioning 10/10 minutes before ischemia (PRE), and two 30/30-second ischemic postconditioning cycles after ischemia and hepatectomy (POS). All animals were subjected to 24-hour reperfusion. Aspartate aminotransferase and alanine aminotransferase activity were measured to evaluate liver damage, and histological analysis, proliferating cell nuclear antigen (PCNA) and regenerated mass liver were used to evaluate liver regeneration. Statistical analyses were performed using ANOVA and Kruskal-Wallis test. ResultsAlanine aminotransferase and aspartate aminotransferase levels were significantly lower in conditioned groups than in the IR group. Regarding mitotic index, IR > control group and HEP (P < .05), PRE and POS were not significantly different from IR, and POS > HEP (P < .05). PCNA analysis showed that IR > HEP (P < .01), PRE < IR (P < .01), and no significant differences were observed between POS and IR groups. No significant differences in regenerated mass liver were observed between conditioned groups and HEP. ConclusionsIschemic postconditioning prevented ischemic injury, promoted greater liver regeneration, and should be further investigated as an alternative better than ischemic preconditioning.