Department of Burns, the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, PR China.
PLoS One. 2013 Jul 11;8(7):e68786. doi: 10.1371/journal.pone.0068786. Print 2013.
High-mobility group box 1 protein (HMGB1), a ubiquitous nuclear protein, drives proinflammatory responses when released extracellularly. It plays a key role as a distal mediator in the development of acute lung injury (ALI). Sodium butyrate, an inhibitor of histone deacetylase, has been demonstrated to inhibit HMGB1 expression. This study investigates the effect of sodium butyrate on burn-induced lung injury. Sprague-Dawley rats were divided into three groups: 1) sham group, sham burn treatment; 2) burn group, third-degree burns over 30% total body surface area (TBSA) with lactated Ringer's solution for resuscitation; 3) burn plus sodium butyrate group, third-degree burns over 30% TBSA with lactated Ringer's solution containing sodium butyrate for resuscitation. The burned animals were sacrificed at 12, 24, and 48 h after burn injury. Lung injury was assessed in terms of histologic changes and wet weight to dry weight (W/D) ratio. Tumor necrosis factor (TNF)-α and interleukin (IL)-8 protein concentrations in bronchoalveolar lavage fluid (BALF) and serum were measured by enzyme-linked immunosorbent assay, and HMGB1 expression in the lung was determined by Western blot analysis. Pulmonary myeloperoxidase (MPO) activity and malondialdehyde (MDA) concentration were measured to reflect neutrophil infiltration and oxidative stress in the lung, respectively. As a result, sodium butyrate significantly inhibited the HMGB1 expressions in the lungs, reduced the lung W/D ratio, and improved the pulmonary histologic changes induced by burn trauma. Furthermore, sodium butyrate administration decreased the TNF-α and IL-8 concentrations in BALF and serum, suppressed MPO activity, and reduced the MDA content in the lungs after severe burn. These results suggest that sodium butyrate attenuates inflammatory responses, neutrophil infiltration, and oxidative stress in the lungs, and protects against remote ALI induced by severe burn, which is associated with inhibiting HMGB1 expression.
高迁移率族蛋白 B1（HMGB1）是一种普遍存在的核蛋白，当其释放到细胞外时会引发促炎反应。它作为急性肺损伤（ALI）发展的远端介质发挥着关键作用。组蛋白去乙酰化酶抑制剂丁酸钠已被证明可以抑制 HMGB1 的表达。本研究探讨了丁酸钠对烧伤诱导性肺损伤的影响。将 Sprague-Dawley 大鼠分为三组：1）假手术组，仅进行假烧伤处理；2）烧伤组，30%以上总体表面积（TBSA）的 III 度烧伤，并用乳酸林格氏液进行复苏；3）烧伤加丁酸钠组，30%以上 TBSA 的 III 度烧伤，用含有丁酸钠的乳酸林格氏液进行复苏。烧伤动物在烧伤后 12、24 和 48 小时处死。通过组织学变化和湿重/干重（W/D）比评估肺损伤。通过酶联免疫吸附试验测量支气管肺泡灌洗液（BALF）和血清中的肿瘤坏死因子（TNF）-α和白细胞介素（IL）-8 蛋白浓度，并通过 Western blot 分析测定肺组织中的 HMGB1 表达。测量肺髓过氧化物酶（MPO）活性和丙二醛（MDA）浓度分别反映肺内中性粒细胞浸润和氧化应激。结果表明，丁酸钠可显著抑制肺组织中 HMGB1 的表达，降低肺 W/D 比，并改善烧伤创伤引起的肺组织学变化。此外，丁酸钠给药可降低 BALF 和血清中 TNF-α和 IL-8 的浓度，抑制 MPO 活性，减少肺组织中 MDA 的含量，从而减轻严重烧伤引起的远隔 ALI。这些结果表明，丁酸钠可减轻肺部的炎症反应、中性粒细胞浸润和氧化应激，并防止严重烧伤引起的远隔性 ALI，这与抑制 HMGB1 的表达有关。
