文献类型： 外文期刊

作者： He, Liang ¹ ; Hao, Lili ² ; Fu, Xin ¹ ; Huang, Mingshu ¹ ; Li, Rui ³ ;

作者机构： 1.Natl Shanghai Ctr New Drug Safety Evaluat & Res, Shanghai 201203, Peoples R China

2.Southwest Univ Nationalities, Coll Life Sci & Technol, Chengdu 610041, Sichuan, Peoples R China

3.Minist Agr, Key Lab Pesticide Residue Detect, State Key Lab Breeding Base Zhejiang Sustainable, Hangzhou 310021, Zhejiang, Peoples R China

4.Zhejiang Acad Agr Sci, Inst Qual & Standard Agroprod, Hangzhou 310021, Zhejiang, Peoples R China

关键词： High-fat;High-cholesterol;Streptozotoncin;Hyperlipidemia;Hypertriglyceridemia;Hypercholesterolemia;Diabetes;Hamsters;Renal injury

期刊名称：BMC NEPHROLOGY （ 影响因子：2.388； 五年影响因子：2.879 ）

ISSN： 1471-2369

年卷期： 2015 年 16 卷

页码：

收录情况： SCI

摘要： Background: Hyperlipidemia is thought to be a major risk factor for the progression of renal diseases in diabetes. Recent studies have shown that lipid profiles are commonly abnormal early on type 2 diabetes mellitus (T2DM) with diabetic nephropathy. However, the early effects of triglyceride and cholesterol abnormalities on renal injury in type 1 diabetes mellitus (T1DM) are not fully understood and require reliable animal models for exploration of the underlying mechanisms. Hamster models are important tools for studying lipid metabolism because of their similarity to humans in terms of lipid utilization and high susceptibility to dietary cholesterol and fat. Methods: Twenty-four male Golden Syrian hamsters (100-110 g) were rendered diabetes by intraperitoneal injections of streptozotocin (STZ) on consecutive 3 days at dose of 30 mg/kg, Ten days after STZ injections, hamsters with a plasma Glu concentration more than 12 mmol/L were selected as insulin deficient ones and divided into four groups (D-C, D-HF, D-HC, and D-HFHC), and fed with commercially available standard rodent chow, high-fat diet, high-cholesterol diet, high-fat and cholesterol diet respectively, for a period of four weeks. Results: After an induction phase, a stable model of renal injury was established with the aspects of early T1DM kidney disease, These aspects were severe hypertriglyceridemia, hypercholesterolemia, proteinuria with mesangial matrix accumulation, upgraded creatinine clearance, significant cholesterol and triglyceride deposition, and increasing glomerular surface area, thickness of basement membrane and mesangial expansion. The mRNA levels of sterol regulatory element binding protein-1c, transforming growth factors-beta, plasminogen activator inhibitor-1, tumor necrosis factor-alpha and interleukin-6 in the D-HFHC group were significantly up-regulated compared with control groups. Conclusions: This study presents a novel, non-transgenic, non-surgical method for induction of renal injury in hamsters, which is an important complement to existing diabetic models for pathophysiological studies in early acute and chronic kidney disease, especially hyperlipidemia. These data suggest that both severe hypertriglyceridemia and hypercholesterolemia can accelerate renal injury in the early development of T1DM.