Department of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Adv Exp Med Biol. 2019;1165:585-604. doi: 10.1007/978-981-13-8871-2_29.
Oxidative stress results from the disruption of the redox system marked by a notable overproduction of reactive oxygen species. There are four major sources of reactive oxygen species, including NADPH oxidases, mitochondria, nitric oxide synthases, and xanthine oxidases. It is well known that renal abnormalities trigger the production of reactive oxygen species by diverse mechanisms under various pathologic stimuli, such as acute kidney injury, chronic kidney disease, nephrotic syndrome, and metabolic disturbances. Mutually, accumulating evidences have identified that oxidative stress plays an essential role in tubulointerstitial fibrosis by myofibroblast activation as well as in glomerulosclerosis by mesangial sclerosis, podocyte abnormality, and parietal epithelial cell injury. Given the involvement of oxidative stress in renal fibrosis, therapies targeting oxidative stress seem promising in renal fibrosis management. In this review, we sketch the updated knowledge of the mechanisms of oxidative stress generation during renal diseases, the pathogenic processes of oxidative stress elicited renal fibrosis and treatments targeting oxidative stress during tubulointerstitial fibrosis and glomerulosclerosis.
氧化应激是由氧化还原系统的破坏引起的,其特征是活性氧物种的显著过度产生。活性氧物种有四个主要来源,包括 NADPH 氧化酶、线粒体、一氧化氮合酶和黄嘌呤氧化酶。众所周知,肾脏异常在各种病理刺激下通过多种机制触发活性氧物种的产生,如急性肾损伤、慢性肾脏病、肾病综合征和代谢紊乱。相互作用的证据表明,氧化应激通过肌成纤维细胞激活在肾小管间质纤维化中发挥重要作用,在肾小球硬化中通过系膜硬化、足细胞异常和壁层上皮细胞损伤发挥作用。鉴于氧化应激与肾纤维化的关系,针对氧化应激的治疗方法在肾纤维化的管理中似乎很有前景。在这篇综述中,我们概述了肾脏疾病中氧化应激产生的机制、氧化应激引起的肾纤维化的发病过程以及针对肾小管间质纤维化和肾小球硬化中氧化应激的治疗方法的最新知识。