Xia Lingya, Yuan Hai, Gao Zhao, Lv Ying, Xu Liang, Hu Fengqi
School of Medicine, Wuhan University of Science and Technology, Wuhan 430065, China.
Department of Nephrology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang 441000, China.
J Toxicol Pathol. 2025 Jan;38(1):17-26. doi: 10.1293/tox.2024-0046. Epub 2024 Sep 11.
Acute kidney injury induced by stings from multiple wasps is a medical emergency and is a driving factor of acute renal dysfunction. Numerous studies have shown that mitochondrial reactive oxygen species (mtROS) play a key role in ischemia-reperfusion injury-, cisplatin-, and sepsis-induced acute kidney injury. However, the role of mtROS and its underlying mechanisms in wasp-venom-induced acute kidney injury remain inconclusive. In this study, we investigated the role and mechanisms of mtROS in mitochondrial damage and inflammation in a mouse model of acute kidney injury induced using wasp venom. Changes in mitochondrial function, transcription factor A (TFAM) expression, and DNA maintenance levels, renal function, stimulator of interferon gene (STING) expression, and inflammatory mediator levels in model mice with or without the mtROS scavenger Mito-Tempo were analyzed . Downregulation of mtROS levels reversed renal damage and mitochondrial dysfunction, and reduced STING expression and inflammation in the kidneys of model mice. The suppression of mtROS levels also improved the decrease in TFAM levels and mitochondrial DNA copy numbers in the kidneys of the model mice. In summary, the existing evidence in this study shows that mtROS contribute significantly to mitochondrial damage and inflammation in acute kidney injury induced by wasp venom.
多只黄蜂蜇伤所致急性肾损伤是一种医疗急症，也是急性肾功能障碍的一个驱动因素。众多研究表明，线粒体活性氧（mtROS）在缺血再灌注损伤、顺铂及脓毒症所致急性肾损伤中起关键作用。然而，mtROS在黄蜂毒液诱导的急性肾损伤中的作用及其潜在机制仍无定论。在本研究中，我们在使用黄蜂毒液诱导的急性肾损伤小鼠模型中，研究了mtROS在线粒体损伤和炎症中的作用及机制。分析了给予或未给予mtROS清除剂Mito-Tempo的模型小鼠的线粒体功能、转录因子A（TFAM）表达、DNA维持水平、肾功能、干扰素基因刺激因子（STING）表达及炎症介质水平的变化。mtROS水平下调可逆转模型小鼠的肾损伤和线粒体功能障碍，并降低模型小鼠肾脏中的STING表达和炎症反应。mtROS水平的抑制还改善了模型小鼠肾脏中TFAM水平和线粒体DNA拷贝数的降低。总之，本研究中的现有证据表明，mtROS在黄蜂毒液诱导的急性肾损伤的线粒体损伤和炎症中起重要作用。
