Jeong Kyung-Hwan, Lee Tae-Won, Ihm Chun-Gyoo, Lee Sang-Ho, Moon Ju-Young, Lim Sung-Jig
Department of Nephrology, School of Medicine, Kyung Hee University, Seoul, Korea.
Am J Nephrol. 2009;29(3):274-82. doi: 10.1159/000158635. Epub 2008 Sep 24.
Oxidative stress and inflammation are implicated in the pathogenesis of diabetic nephropathy. Because sildenafil citrate (Viagra) has variable cardiovascular benefits, including antioxidative and immunomodulating effects, we investigated its influence on oxidative stress and inflammation in diabetic rat kidney.
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.
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. Sildenafil-treated 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.
Sildenafil treatment may attenuate renal damage by ameliorating oxidative and inflammatory injuries in diabetic rats.
氧化应激和炎症与糖尿病肾病的发病机制有关。由于枸橼酸西地那非（万艾可）具有多种心血管益处，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。
链脲佐菌素诱导的糖尿病大鼠接受西地那非治疗（饮水中含3 mg/kg/天）或不接受治疗（饮用未加药的水），持续8周，并与年龄匹配的非糖尿病动物进行比较。我们评估了肾脏中的8-羟基脱氧鸟苷（8-OHdG；用于评估氧化性DNA损伤）、诱导型一氧化氮合酶（iNOS）和硝基酪氨酸（用于评估过量一氧化氮生成和过氧亚硝酸盐形成），以及代表性趋化因子[单核细胞趋化蛋白-1，MCP-1；用于评估炎症和单核细胞/巨噬细胞浸润（ED-1）]。
接受西地那非治疗的大鼠肾脏与体重之比低于未治疗的糖尿病大鼠。西地那非治疗后，糖尿病大鼠的尿白蛋白排泄显著降低，而收缩压无变化。接受西地那非治疗的大鼠尿和肾皮质中的8-OHdG水平显著低于未接受西地那非治疗的组。给予西地那非显著减轻了肾脏硝基酪氨酸蛋白表达的增加、肾小球和肾小管间质中iNOS和ED-1阳性染色以及肾小管间质中硝基酪氨酸染色。西地那非组皮质MCP-1 RNA表达显著低于未接受西地那非治疗的组。
西地那非治疗可能通过改善糖尿病大鼠的氧化和炎症损伤来减轻肾脏损害。
