Gender-specific development of liver injury and necroinflammation over time after hepatic ischaemia-reperfusion in a mouse model

Introduction Ischaemia and reperfusion injury (IRI) are still one of the main problems after liver transplantation. Although many new findings on the pathomechnism of IRI have been elucidated over the past decades, little is known about how the course of the injury compares between the genders.

Methods In a hepatic IRI mouse model, we used 8-12 week old males and females of the C57BL6 strain. Part oft the liver was clamped for 45 min (or 90min) and reperfused after defined times (0 min, 20 min, 1 h, 2 h, 6 h, 24 h). Serum and liver tissue were analysed (ALT and AST; immunohistochemistry of CD3, Gr-1, NKp46 cells). Furthermore, cell death signalling pathways were analysed by rtPCR and Western blot.

Results We have seen significant increases in serum ALT in both genders after reperfusion at early time points. Females showed higher ALT levels at 1h post-reperfusion (400 U/l vs. 200 U/l), while in males higher ALT levels were detected at 48h (86 U/l vs. 37 U/l). CD3+T cells were found to be higher in the female animals (2.6 vs. 7.8 cells/hpf), while no sex-specific differences were found in NKp46+and Gr-1+cells. In addition, we detected gender-specific differences in cell death activation (GPX4, ACSL4, PARP).

Discussion The early phase of hepatic ischaemia and reperfusion appears to develop differently in male and female mice. In particular, T cell-mediated necroinflammation and cell death appears to be significantly different, which may be important for the post-transplantation outcome.

Publication History

Article published online:
20 January 2025