Effects of Sildenafil on Oxidative and Inflammatory Injuries of the Kidney in Streptozotocin-Induced Diabetic Rats
Effects of Sildenafil on Oxidative and Inflammatory Injuries of the Kidney in Streptozotocin-Induced Diabetic Rats
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DOI：
10.1159/000158635
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发表时间：
2009-01-01
影响因子：
4.2
通讯作者：
Lim, Sung-Jig
中科院分区：
文献类型：
--
作者：
Jeong, Kyung-Hwan;Lee, Tae-Won;Lim, Sung-Jig
背景：氧化应激和炎症参与糖尿病肾病的发病机制。由于西地那非柠檬酸盐（伟哥（R））具有不同的心血管益处，包括抗氧化和免疫调节作用，我们研究了其对糖尿病大鼠肾脏氧化应激和炎症的影响。研究方法：链脲佐菌素诱导的糖尿病大鼠接受西地那非（3 mg/kg/天，在饮用水中）或不接受西地那非（未给药的水）8周，并与年龄匹配的非糖尿病动物进行比较。我们评价了8-羟基脱氧鸟苷（8-OHdG;用于氧化性DNA损伤）、诱导型一氧化氮合酶（iNOS）和硝基酪氨酸（用于过量NO产生和过氧亚硝酸盐形成）以及肾脏中的代表性趋化因子[单核细胞趋化蛋白-1，MCP-1;用于炎症和单核细胞/巨噬细胞浸润（艾德-1）]。结果：西地那非治疗的糖尿病大鼠的肾体重比低于未治疗的糖尿病大鼠。糖尿病大鼠经西地那非治疗后尿白蛋白排泄量显著降低，而收缩压无明显变化。西地那非治疗组大鼠的尿和肾皮质8-OHdG水平显著低于非西地那非组。西地那非给药显著减弱了肾脏硝基酪氨酸蛋白表达的增加，肾小球和肾小管中iNOS和艾德-1染色阳性，以及肾小管中硝基酪氨酸染色。西地那非组皮质MCP-1 RNA表达显著低于非西地那非组。结论：西地那非治疗可能通过减轻糖尿病大鼠的氧化损伤和炎症损伤而减轻肾脏损害。版权所有（c）2008 S. Karger AG，巴塞尔
Background: Oxidative stress and inflammation are implicated in the pathogenesis of diabetic nephropathy. Because sildenafil citrate (Viagra (R)) has variable cardiovascular benefits, including antioxidative and immunomodulating effects, we investigated its influence on oxidative stress and inflammation in diabetic rat kidney. Methods: Streptozotocin-induced diabetic rats received sildenafil (3 mg/kg/day in drinking water) or not (undosed water) for 8 weeks and were compared to age-matched nondiabetic animals. We evaluated 8-hydroxydeoxyguanosine (8-OHdG; for oxidative DNA damage), inducible nitric oxide synthase (iNOS) and nitrotyrosine (for excessive NO production and peroxynitrite formation), and representative chemoattractants [monocyte chemotactic protein-1, MCP-1; for inflammation and monocyte/ macrophage infiltrations (ED-1)] in the kidney. Results: Sildenafil-treated rats had a lower kidney-to-body weight ratio than untreated diabetic rats. Urinary albumin excretion in diabetic rats decreased significantly after sildenafil treatment without changes in systolic blood pressure. Sildenafiltreated rats had significantly lower urinary and renal cortical 8-OHdG levels than the nonsildenafil group. Sildenafil administration significantly attenuated the increased renal nitrotyrosine protein expression, positive iNOS and ED-1 staining in glomeruli and tubulointerstitium, and nitrotyrosine staining in tubulointerstitium. Cortical MCP-1 RNA expression in the sildenafil group was significantly lower than in the nonsildenafil group. Conclusions: Sildenafil treatment may attenuate renal damage by ameliorating oxidative and inflammatory injuries in diabetic rats. Copyright (c) 2008 S. Karger AG, Basel