Quercetin improves lipid metabolism via SCAP-SREBP2-LDLr signaling pathway in early stage diabetic nephropathy
Quercetin improves lipid metabolism via SCAP-SREBP2-LDLr signaling pathway in early stage diabetic nephropathy
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DOI：
10.2147/dmso.s195456
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发表时间：
2019-01-01
期刊：
影响因子：
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通讯作者：
Li, Nan
中科院分区：
文献类型：
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作者：
Jiang, Xiyuan;Yu, Jiangyi;Li, Nan
目的：槲皮素是分布最广泛的黄酮类化合物，已被证明具有多种特性并对各种代谢疾病具有有益作用。因此，我们的目的是研究槲皮素调节肾脏脂质积聚和改善2型糖尿病模型Lepr（db）/Lepr（db）（db/db）小鼠早期糖尿病肾损伤的潜在机制。在干预后第10周结束时处死小鼠;相似数量的db/db和db/m小鼠用作对照。在实验研究期间，每天观察动物的一般状态;每两周测量一次体重和血糖浓度。用全自动生化分析仪测定脂代谢生化指标。使用市售试剂盒进行肾功能参数测定。H&E染色和油红O染色分别显示早期肾脏组织学改变和脂质积聚。Western blot检测糖尿病小鼠肾脏低密度脂蛋白受体（LDLr）-SREBP-2-SREBP cSCAP信号通路中关键蛋白的表达。与糖尿病对照组相比，槲皮素不仅能改善白蛋白尿和尿白蛋白/肌酐比值，还能降低血尿素氮和血糖、血清胆固醇、甘油三酯和低密度脂蛋白胆固醇，而对糖尿病db/db小鼠的高密度脂蛋白胆固醇无明显影响。结论：槲皮素可能通过SCAP-SREBP 2-LDLr信号通路改善脂代谢，从而安全有效地减轻糖尿病早期肾损伤。
Purpose: Quercetin, the most widely distributed flavonoid, has been shown to have multiple properties and beneficial effects on various metabolic diseases. Thus, our aim was to investigate the underlying mechanism whereby quercetin regulates renal lipid accumulation and ameliorates early diabetic renal injuries in Lepr(db)/Lepr(db) (db/db) mice, a model of type 2 diabetes.Methods: db/db mice were administered either 50 mg/kg or 100 mg/kg quercetin by oral gavage once a day to evaluate its effects on early stage diabetic nephropathy; mice were sacrificed at the end of the 10th week after intervention; a similar number of db/db and db/m mice were used as controls. During the experimental study, the general status of the animals was observed daily; body weight and blood glucose concentrations were measured at bi-weekly intervals. Biochemical parameters of lipid metabolism were measured by automatic biochemical analyzer. Renal function parameters were performed using commercial kits. Early renal histological changes and lipid accumulation were demonstrated by H&E staining and Oil-Red-O staining, respectively. Moreover, the expression of key proteins in the low-density lipoprotein receptors (LDLr)-SREBP-2-SREBP cSCAP signaling pathway in the kidneys of diabetic mice was detected by Western blot assay.Results: Compared with diabetic controls, quercetin not only ameliorated albuminuria and urinary albumin-to-creatinine ratio, but also decreased blood urea nitrogen and glucose, serum cholesterol, triglycerides, and low-density lipoprotein cholesterol, whereas it had no remarkable effect on the high-density lipoprotein cholesterol in diabetic db/db mice. Additionally, the evidently down regulated expression of (LDLr), HMGCR, SREBP-2, and SCAP subsequently attenuated the renal lipid profile change and lipid droplet accumulation, resulting in the alleviation of renal injury of db/db mice.Conclusion: Quercetin safely and efficiently alleviates early diabetic renal injuries, possibly through improving the lipid metabolism via SCAP-SREBP2-LDLr signaling pathway.