Jiang Xiyuan, Yu Jiangyi, Wang Xin, Ge Jing, Li Nan
The First Clinical Medical School, Nanjing University of Chinese Medicine, Jiangsu 210029, People's Republic of China.
Eodocrinology Department, KunShan Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu, 215300, People's Republic of China.
Diabetes Metab Syndr Obes. 2019 May 30;12:827-839. doi: 10.2147/DMSO.S195456. eCollection 2019.
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/Lepr (db/db) mice, a model of type 2 diabetes. 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. 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. Quercetin safely and efficiently alleviates early diabetic renal injuries, possibly through improving the lipid metabolism via SCAP-SREBP2-LDLr signaling pathway.
槲皮素是分布最广泛的黄酮类化合物，已被证明对各种代谢性疾病具有多种特性和有益作用。因此，我们的目的是研究槲皮素调节Lepr/Lepr（db/db）小鼠（一种2型糖尿病模型）肾脂质蓄积并改善早期糖尿病肾损伤的潜在机制。通过每天一次口服灌胃给予db/db小鼠50mg/kg或100mg/kg槲皮素，以评估其对早期糖尿病肾病的影响；干预10周结束时处死小鼠；使用数量相近的db/db和db/m小鼠作为对照。在实验研究期间，每天观察动物的一般状况；每两周测量一次体重和血糖浓度。使用自动生化分析仪测量脂质代谢的生化参数。使用商用试剂盒检测肾功能参数。分别通过苏木精-伊红（H&E）染色和油红O染色显示早期肾脏组织学变化和脂质蓄积。此外，通过蛋白质印迹法检测糖尿病小鼠肾脏中低密度脂蛋白受体（LDLr）-固醇调节元件结合蛋白-2（SREBP-2）-SREBP裂解激活蛋白（cSCAP）信号通路关键蛋白的表达。与糖尿病对照组相比，槲皮素不仅改善了蛋白尿和尿白蛋白与肌酐比值，还降低了血尿素氮和血糖、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没有显著影响。此外，LDLr、3-羟基-3-甲基戊二酰辅酶A还原酶（HMGCR）、SREBP-2和cSCAP表达的明显下调随后减弱了肾脏脂质谱变化和脂滴蓄积，从而减轻了db/db小鼠的肾损伤。槲皮素可能通过SCAP-SREBP2-LDLr信号通路改善脂质代谢，从而安全有效地减轻早期糖尿病肾损伤。
