Effects of hydrogen on lung injury in wild-type and Nrf2 gene knockout mice: relationship with Nrf2/HO-1/HMGB1 pathway

Results: Compared with Sham groups, the 7-day survival rates of WT and Nrf2-KO mice in CLP groups were significantly lowered [WT: 0% (0/20) vs. 100% (20/20), Nrf2-KO: 0% (0/20) vs. 100% (0/20), both P < 0.05]; the 7-day survival rates of CLP+H2 group in WT mice were significantly higher than those of CLP group [40% (8/20) vs. 0% (0/20), P 0.05]. In WT mice, compared with Sham group, the activities of SOD and CAT in lung tissue of CLP group were decreased significantly [SOD (kU/g): 131.30±28.21 vs. 251.00±22.84, CAT (kU/g): 13.43±1.52 vs. 20.76±1.63, both P < 0.01], the MDA content, the expressions of HO-1 and HMGB1 were increased significantly [MDA (μmol/g): 6.26±1.18 vs. 4.16±0.58, HO-1/β-actin: 0.160±0.045 vs. 0.023±0.005, HMGB1/β-actin: 0.656±0.055 vs. 0.005±0.001, all P < 0.05]. Compared with CLP group, the activities of SOD, CAT and HO-1 expression in lung tissue of CLP+H2 group were significantly increased [SOD (kU/g): 220.32±35.06 vs. 131.30±28.21, CAT (kU/g): 18.95±2.49 vs. 13.43±1.52, HO-1/β-actin: 0.376±0.025 vs. 0.160±0.045, all P < 0.01], while the MDA contents and HMGB1 expressions were significantly decreased [MDA (μmol/g): 4.26±0.75 vs. 6.26±1.18, HMGB1/β-actin: 0.343±0.040 vs. 0.656±0.055, both P < 0.05]. In Nrf2-KO mice, compared with Sham group, the activity of CAT in CLP group was significantly lowered (kU/g: 12.28±1.49 vs. 19.11±1.53, P < 0.01), MDA contents and the expressions of HO-1 and HMGB1 were significantly increased [MDA (μmol/g): 6.85±0.54 vs. 4.59±0.50, HO-1/β-actin: 0.063±0.005 vs. 0.021±0.003, HMGB1/β-actin: 0.713±0.035 vs. 0.005±0.001, all P 0.05). There was no significant difference in above parameters between CLP+H2 group and CLP group. Conclusions: H2 inhibits lung injury in septic mice through Nrf2/HO-1/HMGB1 pathway. Nrf2 plays a major role in the treatment of septic lung injury by H2.