Objective:To investigate the role of calcium-binding protein S100A9 in acute lung injury induced by hepatic ischemia-reperfusion (HIR) in mice, and to explore its relationship with nuclear factor erythroid 2-related factor 2 (Nrf2).Methods:A total of 12 specific pathogen-free (SPF) male wild-type (WT) and 12 S100A9 knockout (S100A9 KO) C57BL/6J mice aged 6~8 weeks and weighing 20-25 g were randomly divided into four groups using a random number table: WT+Sham group, S100A9 KO+Sham group, WT+HIR group, and S100A9 KO+HIR group ( n=6 per group). The HIR model was established by clamping the portal vein and hepatic artery of the left and median liver lobes for 60 minutes followed by reperfusion. At 6 hours post-reperfusion, mice were anesthetized again, and blood samples were collected from the inferior vena cava. Both lungs were harvested. The lung wet-to-dry (W/D) weight ratio was measured. Hematoxylin and eosin (HE) staining was used to assess histopathological changes and calculate lung injury scores. The levels of inflammatory markers—S100A9, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) —as well as oxidative stress indicators including myeloperoxidase (MPO), reactive oxygen species (ROS), malondialdehyde (MDA), and superoxide dismutase (SOD) in serum and lung tissue were measured. Western blotting was used to assess the expression levels of nuclear and cytoplasmic Nrf2, and cytoplasmic HO-1. Results:Compared with the WT+Sham group, both the WT+HIR and S100A9 KO+HIR groups showed significantly increased lung injury scores, W/D ratio, TNF-α, IL-6, ROS, MPO, and MDA levels (all P<0.05). Compared with the WT+HIR group, the S100A9 KO+HIR group exhibited significantly reduced levels of these indicators (all P<0.05). Moreover, the S100A9 KO+HIR group showed elevated nuclear Nrf2 expression and decreased cytoplasmic Nrf2 expression, accompanied by increased expression of HO-1, Gclm, Gclc, and Nqo1 (all P<0.05). Conclusion:Upregulation of S100A9 is involved in the development of HIR-induced acute lung injury, possibly through inhibition of Nrf2 nuclear translocation.

Objective:To investigate the role of calcium-binding protein S100A9 in acute lung injury induced by hepatic ischemia-reperfusion (HIR) in mice, and to explore its relationship with nuclear factor erythroid 2-related factor 2 (Nrf2).Methods:A total of 12 specific pathogen-free (SPF) male wild-type (WT) and 12 S100A9 knockout (S100A9 KO) C57BL/6J mice aged 6~8 weeks and weighing 20-25 g were randomly divided into four groups using a random number table: WT+Sham group, S100A9 KO+Sham group, WT+HIR group, and S100A9 KO+HIR group ( n=6 per group). The HIR model was established by clamping the portal vein and hepatic artery of the left and median liver lobes for 60 minutes followed by reperfusion. At 6 hours post-reperfusion, mice were anesthetized again, and blood samples were collected from the inferior vena cava. Both lungs were harvested. The lung wet-to-dry (W/D) weight ratio was measured. Hematoxylin and eosin (HE) staining was used to assess histopathological changes and calculate lung injury scores. The levels of inflammatory markers—S100A9, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) —as well as oxidative stress indicators including myeloperoxidase (MPO), reactive oxygen species (ROS), malondialdehyde (MDA), and superoxide dismutase (SOD) in serum and lung tissue were measured. Western blotting was used to assess the expression levels of nuclear and cytoplasmic Nrf2, and cytoplasmic HO-1. Results:Compared with the WT+Sham group, both the WT+HIR and S100A9 KO+HIR groups showed significantly increased lung injury scores, W/D ratio, TNF-α, IL-6, ROS, MPO, and MDA levels (all P<0.05). Compared with the WT+HIR group, the S100A9 KO+HIR group exhibited significantly reduced levels of these indicators (all P<0.05). Moreover, the S100A9 KO+HIR group showed elevated nuclear Nrf2 expression and decreased cytoplasmic Nrf2 expression, accompanied by increased expression of HO-1, Gclm, Gclc, and Nqo1 (all P<0.05). Conclusion:Upregulation of S100A9 is involved in the development of HIR-induced acute lung injury, possibly through inhibition of Nrf2 nuclear translocation.