Department of Plastic Surgery, The Second Affiliated Hospital Zhejiang University School of Medicine, Hangzhou 310009, Zhejiang, China.
Department of Hand and Plastic Surgery, First People's Hospital of Yuhang District, Hangzhou 311100, Zhejiang, China.
Life Sci. 2021 Jul 1;276:119095. doi: 10.1016/j.lfs.2021.119095. Epub 2021 Jan 23.
Deep burn-wounds undergo a dynamic progression in the initial or periburn area after insults, and the zone of stasis is the crucial region suffering the deterioration, considered as salvageable. Few studies explored the role of mitochondria in this process. This study is to clarify a possible "built-in" protection of mitophagy.
A classic "comb" scald rat model was established. Histological and blood-flow observation were processed based on hematoxylin-eosin staining and laser analysis. Oxidative and apoptotic status were analyzed by commercial kits. Transmission-electron microscope, immunofluorescence staining, and western blot were applied to detect the mitophagy in the zone of stasis and potential regulators. Adenovirus-based gene-silence contributed to determine the role of HIF-1α as a regulatory mediator.
We found that burn-caused typical ischemia and histological deterioration in the zone of stasis, in parallel with increases in oxidative stress and apoptosis. Mitochondrial damage was involved in the aforementioned changes. Furthermore, we detected mitophagy in burn-wounds, which was contradictory to the burn-wound conversion. HIF-1α expression was closely related to the level of mitophagy, while BNIP3 and PARKIN are involved downstream.
We demonstrate that burn-induced mitochondrial impairment contributes to the mobilization of injurious mechanisms in the zone of stasis and that mitophagy provides a beneficial way to protect against burn-wound progression via the elimination of damaged mitochondria. Our findings offer insights into mitochondrial quality control in burn-wound progression and suggest the novel concept that HIF-1α may be a therapeutic target due to its possible regulation on BNIP3- or PARKIN-mediated mitophagy.
深度烧伤创面在创伤后初始或烧伤周边区域经历动态进展，而淤血区是恶化的关键区域，被认为是可挽救的。很少有研究探讨线粒体在此过程中的作用。本研究旨在阐明可能存在的“内在”自噬保护机制。
建立经典的“梳子”烫伤大鼠模型。基于苏木精-伊红染色和激光分析进行组织学和血流观察。通过商业试剂盒分析氧化应激和细胞凋亡状态。应用透射电镜、免疫荧光染色和 Western blot 检测淤血区的自噬和潜在调节因子。腺病毒介导的基因沉默有助于确定 HIF-1α作为调节介质的作用。
我们发现烧伤引起的典型缺血和淤血区的组织学恶化，同时伴有氧化应激和细胞凋亡增加。线粒体损伤参与了上述变化。此外，我们在烧伤创面中检测到自噬，这与烧伤创面的转化相反。HIF-1α表达与自噬水平密切相关，而 BNIP3 和 PARKIN 则参与下游过程。
我们证明烧伤诱导的线粒体损伤导致淤血区损伤机制的动员，自噬通过消除受损线粒体提供了一种有益的方式来防止烧伤创面进展。我们的发现为烧伤创面进展中线粒体质量控制提供了新的见解，并提出了一个新的概念，即 HIF-1α 可能通过其对 BNIP3 或 PARKIN 介导的自噬的调节成为一种治疗靶点。
