Charlton Amelia, Garzarella Jessica, Jandeleit-Dahm Karin A M, Jha Jay C
Department of Diabetes, Central Clinical School, Monash University, Melbourne 3004, Australia.
Institute for Clinical Diabetology, German Diabetes Centre, Leibniz Centre for Diabetes Research at Heinrich Heine University, Dusseldorf 40225, Germany.
Biology (Basel). 2020 Dec 30;10(1):18. doi: 10.3390/biology10010018.
Oxidative stress and inflammation are considered major drivers in the pathogenesis of diabetic complications, including renal and cardiovascular disease. A symbiotic relationship also appears to exist between oxidative stress and inflammation. Several emerging therapies target these crucial pathways, to alleviate the burden of the aforementioned diseases. Oxidative stress refers to an imbalance between reactive oxygen species (ROS) and antioxidant defenses, a pathological state which not only leads to direct cellular damage but also an inflammatory cascade that further perpetuates tissue injury. Emerging therapeutic strategies tackle these pathways in a variety of ways, from increasing antioxidant defenses (antioxidants and Nrf2 activators) to reducing ROS production (NADPH oxidase inhibitors and XO inhibitors) or inhibiting the associated inflammatory pathways (NLRP3 inflammasome inhibitors, lipoxins, GLP-1 receptor agonists, and AT-1 receptor antagonists). This review summarizes the mechanisms by which oxidative stress and inflammation contribute to and perpetuate diabetes associated renal and cardiovascular disease along with the therapeutic strategies which target these pathways to provide reno and cardiovascular protection in the setting of diabetes.
氧化应激和炎症被认为是糖尿病并发症（包括肾脏疾病和心血管疾病）发病机制的主要驱动因素。氧化应激和炎症之间似乎也存在共生关系。几种新兴疗法针对这些关键途径，以减轻上述疾病的负担。氧化应激是指活性氧（ROS）与抗氧化防御之间的失衡，这种病理状态不仅会导致细胞直接损伤，还会引发炎症级联反应，进一步加剧组织损伤。新兴的治疗策略通过多种方式应对这些途径，从增强抗氧化防御（抗氧化剂和Nrf2激活剂）到减少ROS生成（NADPH氧化酶抑制剂和XO抑制剂）或抑制相关炎症途径（NLRP3炎性小体抑制剂、脂氧素、GLP-1受体激动剂和AT-1受体拮抗剂）。本综述总结了氧化应激和炎症导致并使糖尿病相关肾脏和心血管疾病持续存在的机制，以及针对这些途径以在糖尿病背景下提供肾脏和心血管保护的治疗策略。
