Liver HIF-1 Alpha Induction Precedes Apoptosis Following Normothermic Ischemia-Reperfusion in Rats

Apoptosis plays an important role in ischemia-reperfusion (I-R) injury during liver transplantation. The hypoxia-inducible factor alpha (HIF-1α) may trigger liver apoptosis following I-R through the induction of hypoxically regulated genes. The aim of this study was to evaluate the effect of normothermic liver I-R on HIF-1α expression and apoptosis in rats. Segmental normothermic ischemia of the liver was induced in rats for 120 minutes. Liver extracts from either ischemic or nonischemic lobes were prepared at 0, 1, 3, and 6 hours after reperfusion. Liver HIF-1α protein expression was examined by Western blot analysis. Liver apoptosis was quantified using terminal deoxynucleotide transferase-mediated deoxyuridine triphosphate nick end labeling assay. Normothermic I-R resulted in a significant (P < .05) increase in liver HIF-1α protein levels 1 and 3 hours after reperfusion. Liver apoptosis was significantly (P < .005) increased at 3 and 6 hours after reperfusion. In conclusion, normothermic liver I-R leads to increased liver expression of HIF-1α and apoptosis.