这篇综述讨论了生理条件下胰腺以及急性胰腺炎、慢性胰腺炎、胰腺癌和糖尿病中的氧化应激和氧化还原信号传导。生理氧化还原稳态动力学主要由 NRF2/KEAP1、NF-κB、蛋白酪氨酸磷酸酶、过氧化物酶体增殖物激活受体-γ 共激活因子 1α (PGC1α) 和正常自噬维持。胰腺中还原型谷胱甘肽的消耗是急性胰腺炎的一个标志，最初伴有二硫键应激，其特征是蛋白质半胱氨酸化但谷胱甘肽氧化不增加。氧化应激、MAPK 和 NF-κB 之间的相互作用会放大炎症级联反应，将 PP2A 和 PGC1α 作为关键的氧化还原调节节点。在急性胰腺炎中，胱硫醚-β合酶的硝化会导致反式硫酸化途径受阻，从而导致同型半胱氨酸水平升高，而 p53 通过下调硫氧还蛋白、PGC1α 和过氧化氧还蛋白 3 来触发胰腺坏死性凋亡。慢性胰腺炎表现出由 NADPH 介导的氧化应激氧化酶 1 和/或 CYP2E1，促进细胞死亡、纤维化和炎症。氧化应激与突变型 KRAS 协同启动和促进胰腺癌的发生。突变的 KRAS 会增加线粒体 ROS，从而引发腺泡到导管的化生并进展为 PanIN。 ROS 维持在足够的水平以促进细胞增殖，同时通过 NADPH 和 GSH 的形成以及 NRF-2、HIF-1/2α 和 CREB ​​的激活避免细胞死亡或衰老。氧化还原信号在 β 细胞的分化、增殖和胰岛素分泌中也发挥着重要作用。然而，ROS 过量产生会促进 1 型和 2 型糖尿病中的 β 细胞功能障碍和细胞凋亡。

This review addresses oxidative stress and redox signaling in the pancreas under physiological conditions as well as in acute pancreatitis, chronic pancreatitis, pancreatic cancer, and diabetes. Physiological redox homeodynamics is maintained mainly by NRF2/KEAP1, NF-κB, protein tyrosine phosphatases, peroxisome proliferator-activated receptor-γ co-activator 1α (PGC1α), and normal autophagy. Depletion of reduced glutathione in the pancreas is a hallmark of acute pancreatitis and is initially accompanied by disulfide stress, which is characterized by protein cysteinylation without increased glutathione oxidation. A cross-talk between oxidative stress, MAPKs, and NF-κB amplifies the inflammatory cascade, acting PP2A and PGC1α as key redox regulatory nodes. In acute pancreatitis, nitration of cystathionine-β synthase causes blockade of the trans-sulfuration pathway leading to increased homocysteine levels, whereas p53 triggers necroptosis in the pancreas through downregulation of sulfiredoxin, PGC1α, and peroxiredoxin 3. Chronic pancreatitis exhibits oxidative distress mediated by NADPH oxidase 1 and/or CYP2E1, which promotes cell death, fibrosis, and inflammation. Oxidative stress cooperates with mutant KRAS to initiate and promote pancreatic adenocarcinoma. Mutant KRAS increases mitochondrial ROS, which trigger acinar-to-ductal metaplasia and progression to PanIN. ROS are maintained at sufficient level to promote cell proliferation, whilst avoiding cell death or senescence through formation of NADPH and GSH, and activation of NRF-2, HIF-1/2α, and CREB. Redox signalling also plays a fundamental role in differentiation, proliferation, and insulin secretion of β-cells. However, ROS overproduction promotes β-cell dysfunction and apoptosis in type 1 and type 2 diabetes.