17 β-Estradiol protects the liver against warm ischemia-reperfusion injury through the Akt / GSK-3 β pathway

Objective: To investigate the mechanism of the protective effect of 17β-Estradiol (E2) on warm ischemiareperfusion (IR) injury in rat model. Methods: 24 Sprague-Dawley (SD) male and 12 SD female rats were randomized into six groups. Sham group (Male, Female, Male+17β-E2), IR group (Male, Female, Male+17β-E2), 6 per group. E2 (4 mg/kg) was used by peritoneal injection in Male+17β-E2 groups 1 h before IR injury. Male and female group received same quantity of saline. The rats were sacrificed at 6 h after I/R, concentration of serum alanine aminotransferase (ALT), histomorphology of liver tissue, apoptotic ratio of hepatic cells, expression level of of p-Akt and p-glycogen synthase kinase-3β (p-GSK-3β) were detected. Results: (1) 6 h after IR injury, the concentration of ALT and apoptotic ratio of hepatic cells in Female and Male+17β-E2 group was significantly lower than in Male group. (2) The degree of hepatic injury in Female and Male+17β-E2 group was lower than in Male group. (3) The activation of p-Akt and p-GSK-3β in Female and Male+17β-E2 group was higher than in Male group. Conclusion: E2 protects the liver against warm IR injury through the Akt/GSK-3β kinase pathway. Estrogen therapy might be a “promising treatment” in clinical settings associated with warm IR injury during hepatectomy.