Chen Fan, Xu Kedong, Han Yimin, Ding Jiachun, Ren Jiaqiang, Wang Yaochun, Ma Zhenhua, Cao Fang
Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Pancreatic Disease Center of Xi'an Jiaotong University, Xi'an, China.
Front Immunol. 2024 Dec 24;15:1503087. doi: 10.3389/fimmu.2024.1503087. eCollection 2024.
Acute pancreatitis (AP) is an inflammatory disease of the pancreas and a complex process involving multiple factors, with mitochondrial damage playing a crucial role. Mitochondrial dysfunction is now considered a key driver in the development of AP. This dysfunction often presents as increased oxidative stress, altered membrane potential and permeability, and mitochondrial DNA damage and mutations. Under stress conditions, mitochondrial dynamics and mitochondrial ROS production increase, leading to decreased mitochondrial membrane potential, imbalanced calcium homeostasis, and activation of the mitochondrial permeability transition pore. The release of mitochondrial DNA (mtDNA), recognized as damage-associated molecular patterns, can activate the cGAS-STING1 and NF-κB pathway and induce pro-inflammatory factor expression. Additionally, mtDNA can activate inflammasomes, leading to interleukin release and subsequent tissue damage and inflammation. This review summarizes the relationship between mitochondria and AP and explores mitochondrial protective strategies in the diagnosis and treatment of this disease. Future research on the treatment of acute pancreatitis can benefit from exploring promising avenues such as antioxidants, mitochondrial inhibitors, and new therapies that target mitochondrial dysfunction.
急性胰腺炎(AP)是胰腺的一种炎症性疾病,是一个涉及多种因素的复杂过程,其中线粒体损伤起着关键作用。线粒体功能障碍现在被认为是AP发生发展的关键驱动因素。这种功能障碍通常表现为氧化应激增加、膜电位和通透性改变以及线粒体DNA损伤和突变。在应激条件下,线粒体动力学和线粒体活性氧生成增加,导致线粒体膜电位降低、钙稳态失衡以及线粒体通透性转换孔激活。线粒体DNA(mtDNA)的释放被认为是损伤相关分子模式,可激活cGAS-STING1和NF-κB途径并诱导促炎因子表达。此外,mtDNA可激活炎性小体,导致白细胞介素释放以及随后的组织损伤和炎症。本综述总结了线粒体与AP之间的关系,并探讨了该疾病诊断和治疗中的线粒体保护策略。未来关于急性胰腺炎治疗的研究可以从探索有前景的途径中受益,如抗氧化剂、线粒体抑制剂以及针对线粒体功能障碍的新疗法。