Department of Oral Biology, Medical College of Georgia, Augusta, GA, USA Department of Pharmacology & Toxicology, Medical College of Georgia, Augusta, GA, USA Vascular Biology Center, Medical College of Georgia, Augusta, GA, USA.
Cardiovasc Ther. 2012 Feb;30(1):49-59. doi: 10.1111/j.1755-5922.2010.00218.x. Epub 2010 Aug 16.
The prevalence of diabetes has dramatically increased worldwide due to the vast increase in the obesity rate. Diabetic nephropathy is one of the major complications of type 1 and type 2 diabetes and it is currently the leading cause of end-stage renal disease. Hyperglycemia is the driving force for the development of diabetic nephropathy. It is well known that hyperglycemia increases the production of free radicals resulting in oxidative stress. While increases in oxidative stress have been shown to contribute to the development and progression of diabetic nephropathy, the mechanisms by which this occurs are still being investigated. Historically, diabetes was not thought to be an immune disease; however, there is increasing evidence supporting a role for inflammation in type 1 and type 2 diabetes. Inflammatory cells, cytokines, and profibrotic growth factors including transforming growth factor-β (TGF-β), monocyte chemoattractant protein-1 (MCP-1), connective tissue growth factor (CTGF), tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1), interleukin-6 (IL-6), interleukin-18 (IL-18), and cell adhesion molecules (CAMs) have all been implicated in the pathogenesis of diabetic nephropathy via increased vascular inflammation and fibrosis. The stimulus for the increase in inflammation in diabetes is still under investigation; however, reactive oxygen species are a primary candidate. Thus, targeting oxidative stress-inflammatory cytokine signaling could improve therapeutic options for diabetic nephropathy. The current review will focus on understanding the relationship between oxidative stress and inflammatory cytokines in diabetic nephropathy to help elucidate the question of which comes first in the progression of diabetic nephropathy, oxidative stress, or inflammation.
由于肥胖率的大幅增加，糖尿病的患病率在全球范围内显著上升。糖尿病肾病是 1 型和 2 型糖尿病的主要并发症之一，目前是终末期肾病的主要原因。高血糖是糖尿病肾病发展的驱动力。众所周知，高血糖会增加自由基的产生，导致氧化应激。虽然氧化应激的增加已被证明有助于糖尿病肾病的发生和进展，但发生这种情况的机制仍在研究中。从历史上看，糖尿病不被认为是一种自身免疫性疾病；然而，越来越多的证据支持炎症在 1 型和 2 型糖尿病中的作用。炎症细胞、细胞因子和促纤维化生长因子，包括转化生长因子-β（TGF-β）、单核细胞趋化蛋白-1（MCP-1）、结缔组织生长因子（CTGF）、肿瘤坏死因子-α（TNF-α）、白细胞介素-1（IL-1）、白细胞介素-6（IL-6）、白细胞介素-18（IL-18）和细胞间黏附分子（CAM），都通过增加血管炎症和纤维化而参与糖尿病肾病的发病机制。糖尿病中炎症增加的刺激因素仍在研究中；然而，活性氧是主要候选物。因此，靶向氧化应激-炎症细胞因子信号可能会改善糖尿病肾病的治疗选择。目前的综述将重点探讨氧化应激与糖尿病肾病中炎症细胞因子之间的关系，以帮助阐明糖尿病肾病进展过程中，是氧化应激还是炎症首先发生的问题。
