高迁移率组蛋白B1在感染致急性肺损伤小鼠中作用的研究

High mobility group box 1 in sepsis induced acute lung injury mice

目的观察高迁移率组蛋白B1(HMGB1)在感染导致急性肺损伤(ALI)中的致炎作用。方法内毒素气管内注射建立感染致ALI小鼠模型,观察ALI病变过程中肺组织HMGB1、白介素1β(IL-1β)、肿瘤坏死因子α(TN Fα)、髓过氧化物酶(M PO)含量和肺泡膜通透性的变化,比较抗-HMGB1抗体干预治疗前后小鼠肺内M PO含量、肺泡膜通透性和肺组织病理学的改变。结果感染致ALI小鼠肺组织HMGB1浓度于模型建立后16 h升高,24 h达高峰,48 h仍显著高于对照组。模型建立后4 h肺组织IL-1β和TN Fα浓度显著升高,随后的16 h到48 h降低,与对照组相比无显著差异。M PO水平于模型建立后4 h达峰值([55.0±3.6)U/g肺组织]。模型建立后16 h肺内伊文兰显著升高,于24 h达高峰([19.7±1.7)g/m L肺组织]。应用抗-HMGB1抗体可以显著降低肺内M PO浓度[抗体应用前(55.0±3.6)U/g肺组织、抗体应用后(21.4±3.5)pg/m L/m g肺组织]、减轻肺内伊文兰含量和肺组织病理损伤。结论 HMGB1具有重要的促炎作用,介导感染致ALI的迟发性炎症反应。

【Objective】 To observe the participation of high mobility group box 1（HMGB1） in the pathogenesis of acute lung injury（ALI） caused by sepsis.【Methods】 The study was carried out by mouse sepsis-primed ALI model after lipopolysaccharide（LPS） injection intratracheally.We measured HMGB1 and tumor necrosis factor-alpha and interleukin-1beta and myeloperoxidase lung concentration and lung leak at the designated time points.We then specific inhibited of HMGB1 activity,and examined the effects of anti-HMGB1.【Results】 Administration of LPS injection intratracheally resulted in HMGB1 an increase by 16 h,and increased further by 24 h.Tumor necrosis factor-alpha and interleukin-1beta increased significantly at 4 h.Myeloperoxidase also increased significantly at 4 h [（55.0±3.6） U/g of lung].Sepsis resulted in the highest lung leak at 24 h.Compared with the ALI mice,blockade of HMGB1 prevented significantly myeloperoxidase [（55.0±3.6） U/g of lung vs（21.4±3.5） U/g of lung],lung leak was also diminished markedly.【Conclusion】 HMGB1 plays a key role as a late mediator in sepsis-primed ALI.