The role of HMGB1 in ischemia/reperfusion injury of lung grafts in rats

Objective To investigate the role of high mobility group box 1 (HMGB1) in ischemia/reperfusion injury of lung grafts in rats. Methods The BALB/c mice were randomly divided into control group, 10 μg HMGB1 group and 100 μg HMGB1 group, 5 mice each group. Each mouse in 10 μg HMGB1 group and 100 μg HMGB1 group was intraperitoneally injected 10 μg and 100 μgrecombinant HMGB1, respectively. The experimental orthotopic lung transplantation model in rats was established by cuff technique, and the rats were randomly divided into transplantation control group, 0.1 mg anti-HMGB1 antibody treatment group and 1.0 mg anti-HMGB1 antibody treatment group, 5 rats in each group. Each rat in 0.1 mg anti-HMGB1 antibody treatment group and 1.0 mg anti-HMGB1 antibody treatment group was intraperitoneally injected 0.1 mg and 1.0 mg anti-HMGB1 antibody, respectively. Wet/dry weight ratio of lung tissue, gene expressions of inflammatory cytokines (TNF-α, ICAM-1, IL-6) in lung tissue, lung histopathologic changes, and arterial blood gas were examined 12 h after the treatment of HMGB1 or antibody. Results The reduced PaO2, increased PaCO2 and wet/dry weight ratio, enhanced gene expressions of TNF-α, ICAM-1 and IL-6were showed, and lung histopathologic changes occured after the mice were injected with recombinant HMGB1 especially in 100 μg HMGB1 group.The other indexes of lung grafts in rats, except ICAM-1 gene expression, all significantly improved in antibody dose-dependently manner.Conclusion HMGB1 participate inin rats,and may be the potential target of preventing ischemia/reperfusion injury of lung grafts.