Department of Medicine and Clinical Science, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Okayama, Japan.
Nephron Exp Nephrol. 2012;121(3-4):e97-e108. doi: 10.1159/000343102. Epub 2013 Jan 10.
BACKGROUND/AIMS: Telmisartan, an angiotensin II type 1 receptor blocker, is widely used to treat hypertension and kidney diseases, including diabetic nephropathy, because of its renoprotective effects. However, the mechanism by which telmisartan prevents proteinuria and renal dysfunction in diabetic nephropathy is still unclear. In this study, we examined the effects of telmisartan against diabetic nephropathy in db/db mice.
Telmisartan was administered at a dose of 5 mg/kg/day for 3 weeks to db/db (diabetic) and db/m (control) mice. Urinary albumin excretion, renal histology, and the gene expression of oxidative stress and inflammatory markers in renal tissue were determined. To evaluate the effects of telmisartan on reactive oxygen species (ROS) production, superoxide was detected by dihydroethidium (DHE) staining in vivo and in vitro.
Telmisartan reduced albuminuria, mesangial matrix expansion, macrophage infiltration, and the expression of ROS markers (NADPH oxidase 4- and 8-hydroxydeoxyguanosine) and inflammatory cytokines (monocyte chemoattractant protein-1, osteopontin, and transforming growth factor-β) in the kidney. DHE staining showed that telmisartan decreased ROS generation in the kidney and in cultured mesangial and proximal tubular epithelial cells.
Taken together, these findings indicate that telmisartan protects against diabetic nephropathy by reducing diabetes-induced oxidative stress.
背景/目的：替米沙坦是一种血管紧张素 II 型 1 型受体阻滞剂，由于其具有肾脏保护作用，被广泛用于治疗高血压和肾脏疾病，包括糖尿病肾病。然而，替米沙坦预防糖尿病肾病蛋白尿和肾功能障碍的机制尚不清楚。在本研究中，我们研究了替米沙坦对 db/db 小鼠糖尿病肾病的作用。
替米沙坦以 5mg/kg/天的剂量连续给药 3 周，用于 db/db（糖尿病）和 db/m（对照）小鼠。测定尿白蛋白排泄、肾脏组织学以及肾脏组织中氧化应激和炎症标志物的基因表达。为评估替米沙坦对活性氧（ROS）产生的影响，通过二氢乙啶（DHE）染色在体内和体外检测超氧。
替米沙坦减少了白蛋白尿、系膜基质扩张、巨噬细胞浸润以及肾脏中 ROS 标志物（NADPH 氧化酶 4 和 8-羟基脱氧鸟苷）和炎症细胞因子（单核细胞趋化蛋白-1、骨桥蛋白和转化生长因子-β）的表达。DHE 染色显示替米沙坦减少了肾脏以及培养的肾小球系膜和近端肾小管上皮细胞中的 ROS 生成。
这些发现表明，替米沙坦通过减少糖尿病引起的氧化应激来预防糖尿病肾病。
