高迁移率族蛋白B1在大鼠移植肺缺血再灌注损伤中的作用

摘要

目的:探讨高迁移率族蛋白B1(HMGB1)在大鼠移植肺缺血再灌注损伤中的作用.方法:BALB/c小鼠随机分为对照组、10 μg HMGB1组和100 μg HMGB1组,每组各5只,后两组每只分别腹腔注射重组HMGB1 10 μg和100 μg.三套管法建立SD大鼠肺移植模型并随机分成单纯移植组、移植加0.1 mg抗HMGB1抗体组和移植加1.0 mg抗HMGB1抗体组,每组各5只,后两组每只分别腹腔注射抗HMGB1抗体0.1和1.0 mg.12 h后观察各组肺组织的湿干重比、炎症介质(TNF-α、ICAM-1、IL-6)基因表达、病理表现及动脉血气变化.结果:注射重组HMGB1后尤其100 μg HMGB1组小鼠PaO2降低,PaCO2、湿干重比升高,TNF-α、ICAM-1、IL-6基因表达增强,肺组织出现病理改变.抗HMGB1抗体处理后,除ICAM-1基因表达外,肺移植大鼠的其他指标均有明显改善,并与抗HMGB1抗体剂量有关.结论:HMGB1在肺移植缺血再灌注损伤中具有重要作用,是肺移植缺血再灌注损伤防治的潜在靶标.%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 μg recombinant 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-HMGBl antibody treatment group and 1.0 mg anti-HMGBl antibody treatment group, 5 rats in each group. Each rat in 0.1 mg anti-HMGBl antibody treatment group and 1.0 mg anti-HMGBl antibody treatment group was intraperitoneally injected 0.1 mg and 1.0 mg anti-HMGBl 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 in in rats, and may be the potential target of preventing ischemia/reperfusion injury of lung grafts.