Department of Burns, The Third Affiliated Hospital of Inner Mongolia Medical University, Burns Institute of Inner Mongolia, Baotou 014010, PR China.
Department of Burn and Plastic Surgery, The First Affiliated Hospital of Soochow University, Suzhou 215006, PR China.
Burns. 2022 Aug;48(5):1213-1220. doi: 10.1016/j.burns.2021.11.009. Epub 2021 Nov 16.
Burns are a common traumatic injuries with considerable morbidity and mortality rates. Post-burn intestinal injuries are closely related to oxidative stress and inflammatory response. The aim of the current study was to investigate the combined effect of sodium butyrate (NaB) and probiotics (PROB) on severe burn-induced oxidative stress and inflammatory response and the underlying mechanism of action. Sprague-Dawley rats with severe burns were treated with NaB with or without PROB. Pathomorphology of skin and small intestine tissue was observed using hematoxylin and eosin staining and severe burn-induced apoptosis in small intestine tissue was examined via terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay. The release of factors related to inflammation was quantified using ELISA kits and qRT-PCR and levels of oxidative stress markers were evaluated using biochemical assays. Furthermore, mitochondrial morphological changes in small intestinal epithelial cells were observed using transmission electron microscopy. In addition, the underlying mechanism associated with the combined effect of NaB and PROB on severe burn-induced oxidative stress and inflammatory response was investigated using western blotting. The combination of NaB and PROB exerted protective effects against severe burn-induced intestinal barrier injury by reducing the levels of diamine oxidase and intestinal fatty acid binding protein. Combined NaB and PROB treatment inhibited severe burn-induced oxidative stress by increasing superoxide dismutase levels and decreasing those of malondialdehyde and myeloperoxidase levels. Severe burn-induced inflammation was suppressed by combined NaB and PROB administration, as demonstrated by the decreased mRNA expression of tumor necrosis factor-α, interleukin-6, interleukin-1β, and high mobility group box-1 in the small intestine. In addition, this study showed that combined NaB and PROB administration increased nuclear factor-erythroid 2-related factor 2 (Nrf2) protein expression and decreased the phosphorylation of nuclear factor (NF)-κB and extracellular signal-regulated kinase 1/2 (ERK 1/2). In conclusion, our findings indicate that combined NaB and PROB treatment may inhibit severe burn-induced inflammation and oxidative stress in the small intestine by regulating HMGB1/NF-κB and ERK1/2/Nrf2 signaling, thereby providing a new therapeutic strategy for intestinal injury induced by severe burn.
烧伤是一种常见的创伤性损伤，具有相当高的发病率和死亡率。烧伤后肠道损伤与氧化应激和炎症反应密切相关。本研究旨在探讨丁酸钠（NaB）和益生菌（PROB）联合应用对严重烧伤诱导的氧化应激和炎症反应的影响及其作用机制。采用 NaB 联合或不联合 PROB 处理严重烧伤大鼠。采用苏木精-伊红染色观察皮肤和小肠组织的病理形态学变化，采用末端脱氧核苷酸转移酶介导的 dUTP 生物素缺口末端标记法检测小肠组织严重烧伤诱导的细胞凋亡。采用 ELISA 试剂盒和 qRT-PCR 定量检测炎症相关因子的释放，采用生化测定法评估氧化应激标志物的水平。此外，采用透射电子显微镜观察小肠上皮细胞中线粒体的形态变化。另外，采用 Western blot 法探讨 NaB 和 PROB 联合作用对严重烧伤诱导的氧化应激和炎症反应的作用机制。结果表明，NaB 和 PROB 联合应用可降低二胺氧化酶和肠脂肪酸结合蛋白的水平，减轻严重烧伤引起的肠道屏障损伤，发挥保护作用。联合 NaB 和 PROB 治疗可通过增加超氧化物歧化酶水平和降低丙二醛和髓过氧化物酶水平抑制严重烧伤诱导的氧化应激。联合 NaB 和 PROB 给药可抑制严重烧伤诱导的炎症，表现为小肠组织肿瘤坏死因子-α、白细胞介素-6、白细胞介素-1β和高迁移率族蛋白 1 基因表达降低。此外，本研究表明，联合 NaB 和 PROB 给药可增加核因子红细胞 2 相关因子 2（Nrf2）蛋白表达，降低核因子（NF）-κB 和细胞外信号调节激酶 1/2（ERK 1/2）的磷酸化。综上所述，本研究结果表明，联合 NaB 和 PROB 治疗可能通过调节 HMGB1/NF-κB 和 ERK1/2/Nrf2 信号通路抑制严重烧伤引起的小肠炎症和氧化应激，为严重烧伤引起的肠道损伤提供新的治疗策略。
