Abstract: Objective To investigate the mechanism of heme oxygenase-1 (HO-1) expression in hepatic sinusoidal endothelial cells promoting liver regeneration and reconstruction after ischemia-reperfusion injury in mice. Methods Sixty male mice were randomly divided into a sham surgery group, a model group, an empty vector group, and a HO-1 transfection group of 15 mice each. Except for the sham surgery group, which only underwent anesthesia and open surgery, the other three groups used the classic liver 70% warm ischemia method to establish a mouse model of liver ischemia-reperfusion injury. After reperfusion, the empty vector group was injected with 200 μL of empty vector virus transfected LSECs via the portal vein, while the HO-1 transfection group was injected with 200 μL of CD31 labeled 2×10⁶/mL HO-1 transfected LSECs via the portal vein. Evaluate liver function indicators [alanine aminotransferase (ALT), aspartate aminotransferase (AST)], serum and liver tissue inflammatory factors [tumor necrosis factor] among different groups of mice- α (TNF- α), Interleukin-1 β (IL-1β), changes in levels of interleukin-6 (IL-6), oxidative stress factors (superoxide dismutase (SOD), malondialdehyde (MDA), hepatocyte growth factor (HGF), apoptotic proteins Bax, Bcl-2, Caspase-3, and nuclear factor E2 related factor 2 (Nrf2) and HO-1 protein expression in the Nrf2/HO-1 signaling pathway were observed in liver tissue. Pathological changes in liver tissue and liver cell apoptosis rate were also observed. Methods RT-PCR assay showed that the mRNA expression of HO-1 in lentivirus carrying HO-1 target gene was significantly higher than that in no-load group (P<0.05). ALT and AST levels in model group, no-load group and HO-1 transfection group were higher than those in sham operation group, while ALT and AST levels in HO-1 transfection group were lower than those in model group and no-load group (P<0.05). There was no difference between model group and no-load group (P>0.05). The levels of TNF-α, IL-1β, IL-6 and MDA in serum and liver tissue of model group, no-load group, and HO-1 transfection group were higher than those of sham operation group, and the level of SOD was decreased (P<0.05). The levels of TNF-α, IL-1β, IL-6 and MDA in serum and liver tissue of HO-1 transfection group were lower than those of model group and no-load group, and SOD was increased (P<0.05). There was no difference between model group and no-load group (P>0.05). The pathological changes and apoptosis rate of hepatocytes in model group, no-load group and HO-1 transfection group were higher than those in sham operation group, while those in HO-1 transfection group were lower than those in model group and no-load group (P<0.05). There was no difference between model group and no-load group (P>0.05). The levels of Bax and Caspase-3 in liver tissues of model group, no-load group, and HO-1 transfection group were higher than those of sham operation group, while HGF and Bcl-2 were decreased (P<0.05). The levels of Bax and Caspase-3 in liver tissue of HO-1 transfection group were lower than those of model group and no-load group, while HGF and Bcl-2 were increased (P<0.05). There was no difference between model group and no-load group (P>0.05). The levels of Nrf2 and HO-1 in liver tissue of model group, no-load group and HO-1 transfection group were lower than those of sham operation group (P<0.05), and the levels of Nrf2 and HO-1 in liver tissue of HO-1 transfection group were higher than those of model group and no-load group (P<0.05). There was no difference between model group and no-load group (P>0.05). Conclusion The transplanted HO-1-transfected LSECs with liver ischemia and reperfusion injury can reduce liver oxidative stress and inflammation, reduce hepatocyte apoptosis, promote liver regeneration and reconstruction, and restore liver function, and the mechanism may be related to the activation of Nrf 2/HO-1 signaling pathway.

Key words: Liver ischemia-reperfusion injury, Liver sinusoidal endothelial cells, Heme oxygenase-1, Liver regeneration