Sodium butyrate inhibits the production of HMGB1 and attenuates severe burn plus delayed resuscitation-induced intestine injury via the p38 signaling pathway
Sodium butyrate inhibits the production of HMGB1 and attenuates severe burn plus delayed resuscitation-induced intestine injury via the p38 signaling pathway
复制标题
丁酸钠通过 p38 信号通路抑制 HMGB1 的产生并减轻严重烧伤和延迟复苏引起的肠道损伤
DOI：
10.1016/j.burns.2018.09.031
复制
发表时间：
2019-05-01
期刊：
影响因子：
2.7
通讯作者：
Chen, Xu-Lin
中科院分区：
文献类型：
--
作者：
Liu, Sheng;Chen, Hong-Ze;Chen, Xu-Lin
背景资料：由高迁移率族蛋白B1（HMGB 1）引发的炎症反应和氧化应激在严重烧伤后肠道损伤中起重要作用。丁酸钠是一种组蛋白去乙酰化酶抑制剂，具有潜在的抗炎特性，可抑制多种疾病中炎症介质如HMGB 1的表达。本研究旨在探讨丁酸钠对严重烧伤延迟复苏大鼠肠道损伤、肠道高迁移率族蛋白1（HMGB 1）和细胞内粘附分子1（ICAM-1）表达、氧化应激及信号转导通路的影响。材料与方法：将五十六只SD大鼠随机分为3组：（1）假烧伤组;（2）烧伤组，造成30%体表面积（TBSA）Ⅲ度烧伤，伤后6、12、36 h分别给予2 ml/kg/TBSA乳酸林格液复苏，（3）烧伤+丁酸钠（SB）组，伤后给予含丁酸钠的乳酸林格液复苏。酶联免疫吸附法测定血浆二胺氧化酶（DAO）浓度。免疫组化法检测肠脂肪酸结合蛋白（I-FABP）和细胞间粘附分子-1（ICAM-1）的表达。Western blot检测肠组织中HMGB 1和p38丝裂原活化蛋白激酶（MAPK）的表达。结果：烧伤组大鼠小肠组织HMGB 1表达较假手术组明显增加，肠组织MDA含量明显升高。丁酸钠能显著抑制烧伤延迟复苏大鼠小肠HMGB 1的表达，降低血浆DAO浓度，减少小肠I-FABP的表达，改善烧伤延迟复苏大鼠小肠组织学改变。丁酸钠治疗还明显降低了严重烧伤延迟复苏大鼠肠道ICAM-1表达和MDA含量的增加，并抑制了肠道p38 MAPK活性。结论：丁酸钠通过抑制p38 MAPK信号转导途径抑制HMGB 1表达，减轻肠道炎症反应和氧化应激，从而减轻烧伤和延迟复苏引起的肠损伤。(C)2018 Elsevier Ltd和ISBI。All rights reserved.
Background: Inflammatory response triggered by high mobility group box-1 (HMGB1) protein and oxidative stress play critical roles in the intestinal injury after severe burn. Sodium butyrate, a histone deacetylase inhibitor, has potential anti-inflammatory properties, inhibiting the expression of inflammatory mediators such as HMGB1 in diverse diseases. This study was designed to investigate the effects of sodium butyrate on severe burn plus delayed resuscitation-induced intestine injury, intestinal expressions of HMGB1 and intracellular adhesion molecule-1 (ICAM-1), oxidative stress, and signal transduction pathway changes in rats.Materials and methods: Fifty-six Sprague-Dawley rats were divided into 3 groups randomly: (1) sham group, animals underwent sham burn; (2) burn group, rats subjected to full-thickness burns of 30% total body surface area (TBSA) and received 2 ml/kg/TBSA lactated Ringer solution for resuscitation at 6, 12, and 36h after burn injury; (3) burn plus sodium butyrate (burn + SB) group, animals received burn injury and lactated Ringer solution with sodium butyrate inside for resuscitation in the same manner. Diamine oxidase (DAO) concentration in plasma was measured by enzyme-linked immunosorbent assay. Intestinal fatty acid binding protein (I-FABP) and ICAM-1 expressions in the intestine were analyzed by immunohistochemical method. HMGB1 and p38 mitogen-activated protein kinase (MAPK) expressions in the intestine tissues were examined by Western blot. The intestinal concentration of malondialdehyde (MDA) was also determined.Results: Intestinal HMGB1 expression was significantly increased in burn group compared with sham group. Sodium butyrate administration significantly inhibited the HMGB1 expression in the intestine, decreased the DAO concentration in plasma, reduced the intestinal I-FABP expression, and improved the intestinal histologic changes induced by burn injury plus delayed resuscitation. Sodium butyrate treatment also markedly reduced the increase of intestinal ICAM-1 expression and MDA content, and inhibited p38 MAPK activity in the intestine of severely burned rats with delayed resuscitation.Conclusions: Sodium butyrate inhibits HMGB1 expression which could be attributed to p38 MAPK signal transduction pathway and decreases intestinal inflammatory responses and oxidative stress, thus attenuates burn plus delayed resuscitation-induced intestine injury. (C) 2018 Elsevier Ltd and ISBI. All rights reserved.