Furukawa Masako, Gohda Tomohito, Tanimoto Mitsuo, Tomino Yasuhiko
Division of Nephrology, Department of Internal Medicine, Juntendo University Faculty of Medicine, Bunkyo-ku, Tokyo, Japan.
ScientificWorldJournal. 2013 Apr 24;2013:928197. doi: 10.1155/2013/928197. Print 2013.
Diabetic nephropathy (DN) is the leading cause of end-stage kidney disease worldwide. However, current treatments remain suboptimal. Many factors, such as genetic and nongenetic promoters, hypertension, hyperglycemia, the accumulation of advanced glycation end products (AGEs), dyslipidemia, and albuminuria/proteinuria itself, influence the progression of this disease. It is important to determine the molecular mechanisms and treatment of this disease. The development of diabetes results in the formation of AGEs, oxidative stress, and the activation of the renin-angiotensin-aldosterone system (RAAS) within the kidney, which promotes progressive inflammation and fibrosis, leading to DN and declining renal function. A number of novel therapies have also been tested in the experimental diabetic model, including exercise, inhibitors of the RAAS (angiotensin type 1 receptor blockers (ARB), angiotensin-converting enzyme (ACE) inhibitors), inhibitors of AGE (pyridoxamine), peroxisome proliferator-activated receptor (PPAR) γ agonists (pioglitazone), inhibitors of lipid accumulation (statins and eicosapentaenoic acid (EPA)), and the vitamin D analogues. This review summarizes the advances in knowledge gained from our studies and therapeutic interventions that may prevent this disease.
糖尿病肾病（DN）是全球终末期肾病的主要原因。然而，目前的治疗方法仍不尽人意。许多因素，如遗传和非遗传启动子、高血压、高血糖、晚期糖基化终产物（AGEs）的积累、血脂异常以及蛋白尿/蛋白尿本身，都会影响这种疾病的进展。确定这种疾病的分子机制和治疗方法很重要。糖尿病的发展会导致肾脏内AGEs的形成、氧化应激以及肾素-血管紧张素-醛固酮系统（RAAS）的激活，从而促进进行性炎症和纤维化，导致糖尿病肾病和肾功能下降。一些新疗法也在实验性糖尿病模型中进行了测试，包括运动、RAAS抑制剂（血管紧张素1型受体阻滞剂（ARB）、血管紧张素转换酶（ACE）抑制剂）、AGE抑制剂（吡哆胺）、过氧化物酶体增殖物激活受体（PPAR）γ激动剂（吡格列酮）、脂质积累抑制剂（他汀类药物和二十碳五烯酸（EPA））以及维生素D类似物。这篇综述总结了我们的研究和可能预防这种疾病的治疗干预措施所取得的知识进展。
