The protective effects of oral low-dose quercetin on diabetic nephropathy in hypercholesterolemic mice.
The protective effects of oral low-dose quercetin on diabetic nephropathy in hypercholesterolemic mice.
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口服低剂量槲皮素对高胆固醇小鼠糖尿病性肾病的保护作用。
DOI：
10.3389/fphys.2015.00247
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发表时间：
2015
影响因子：
4
通讯作者：
Vasquez EC
中科院分区：
文献类型：
--
作者：
Gomes IB;Porto ML;Santos MC;Campagnaro BP;Gava AL;Meyrelles SS;Pereira TM;Vasquez EC
目的：糖尿病肾病（DN）是慢性肾脏病的最重要原因之一，并且DN的发病率在全球范围内呈上升趋势。考虑到我们之前的报告 (Gomes 等人) 表明口服低剂量槲皮素 (10 mg/Kg) 的长期治疗在 DN C57BL/6J 模型中表现出抗氧化、抗凋亡和肾脏保护作用，我们使用载脂蛋白 E 缺陷型小鼠 (apoE−/−) 研究了这种黄酮类化合物是否也对并发 DN 和自发性动脉粥样硬化具有有益作用。方法：使用链脲佐菌素在雄性 apoE−/− 小鼠（8 周龄）中诱导糖尿病（100 mg/kg/天，3 天）。 6周后，将小鼠随机分为DQ：用槲皮素治疗的糖尿病apoE−/−小鼠（10 mg/kg/天，4周，n = 8），DV：用载体治疗的糖尿病ApoE−/−小鼠（n = 8）和ND：未治疗的非糖尿病小鼠（n = 8）。结果：槲皮素治疗减少了多尿（~30%；p < 0.05）、血糖（~25%，p < 0.05），使高甘油三酯血症正常化。此外，这种生物类黄酮可减少肌酐血症（约 30%，p < 0.01）并减少蛋白尿，但未达到正常水平。我们还观察到对肾脏结构变化的保护作用，包括肾小球硬化指数和肾脏重量/体重的正常化。结论：我们的数据显示，槲皮素治疗通过诱导生化变化（降低血糖和甘油三酯血清水平）和减少肾小球硬化，显着降低高胆固醇血症小鼠的 DN。因此，这项研究强调了槲皮素作为 DN 替代治疗选择的相关性，包括与血脂异常相关的糖尿病。
Aims: Diabetic nephropathy (DN) is one of the most important causes of chronic renal disease, and the incidence of DN is increasing worldwide. Considering our previous report (Gomes et al.,) indicating that chronic treatment with oral low-dose quercetin (10 mg/Kg) demonstrated anti-oxidative, anti-apoptotic and renoprotective effects in the C57BL/6J model of DN, we investigated whether this flavonoid could also have beneficial effects in concurrent DN and spontaneous atherosclerosis using the apolipoprotein E-deficient mouse (apoE−/−). Methods: Streptozotocin was used to induce diabetes (100 mg/kg/day, 3 days) in male apoE−/− mice (8 week-old). After 6 weeks, the mice were randomly separated into DQ: diabetic apoE−/− mice treated with quercetin (10 mg/kg/day, 4 weeks, n = 8), DV: diabetic ApoE−/− mice treated with vehicle (n = 8) and ND: non-treated non-diabetic mice (n = 8). Results: Quercetin treatment diminished polyuria (~30%; p < 0.05), glycemia (~25%, p < 0.05), normalized the hypertriglyceridemia. Moreover, this bioflavonoid diminished creatininemia (~30%, p < 0.01) and reduced proteinuria but not to normal levels. We also observed protective effects on the renal structural changes, including normalization of the index of glomerulosclerosis and kidney weight/body weight. Conclusions: Our data revealed that quercetin treatment significantly reduced DN in hypercholesterolemic mice by inducing biochemical changes (decrease in glucose and triglycerides serum levels) and reduction of glomerulosclerosis. Thus, this study highlights the relevance of quercetin as an alternative therapeutic option for DN, including in diabetes associated with dyslipidemia.