Telmisartan Attenuates Diabetic Nephropathy by Suppressing Oxidative Stress in db/db Mice
Telmisartan Attenuates Diabetic Nephropathy by Suppressing Oxidative Stress in db/db Mice
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DOI：
10.1159/000343102
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发表时间：
2013-01
影响因子：
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通讯作者：
Chikage Sato-Horiguchi;D. Ogawa;J. Wada;H. Tachibana;Ryo Kodera;Jun Eguchi;A. Nakatsuka;N. Terami;K. Shikata;H. Makino
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文献类型：
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作者：
Chikage Sato-Horiguchi;D. Ogawa;J. Wada;H. Tachibana;Ryo Kodera;Jun Eguchi;A. Nakatsuka;N. Terami;K. Shikata;H. Makino
背景/目标：替米沙坦是一种血管紧张素II 1型受体阻滞剂，由于其肾脏保护作用，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不全的机制尚不清楚。在这项研究中，我们检查了替米沙坦对db/db小鼠糖尿病肾病的影响。方法：以5 mg/kg/d的剂量对db/db（糖尿病）和db/m（对照）小鼠给予替米沙坦3周。测定尿白蛋白排泄、肾组织学、肾组织氧化应激和炎症标志物的基因表达。为了评价替米沙坦对活性氧（ROS）产生的影响，在体内和体外通过二氢乙锭（DHE）染色检测超氧化物。结果如下：替米沙坦可减少蛋白尿、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）和炎性细胞因子（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和培养的系膜和近端肾小管上皮细胞中的ROS生成。结论：综上所述，这些结果表明，替米沙坦通过减少糖尿病诱导的氧化应激来预防糖尿病肾病。
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. Methods: 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. Results: 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. Conclusions: Taken together, these findings indicate that telmisartan protects against diabetic nephropathy by reducing diabetes-induced oxidative stress.