Department of Veterans Affairs, Lexington, KY, USA.
J Lipid Res. 2010 Jun;51(6):1464-70. doi: 10.1194/jlr.M002972. Epub 2010 Jan 28.
Hyperlipidemia is a risk factor for development and progression of diabetic nephropathy. However, it is not known if reduction of hyperlipidemia is protective against progression of disease. The goal of this study was to determine if reduction of hypercholesterolemia could limit progression of diabetic nephropathy. Diabetic and nondiabetic LDL receptor deficient (LDLR(-/-)) mice were fed diets containing either no cholesterol (0%) or high cholesterol (0.12%) for 36 weeks. One group each of diabetic and nondiabetic mice were fed the high-cholesterol diet for 26 weeks then changed to the 0% cholesterol diet for the last 10 weeks. Consumption of the high-cholesterol diet exacerbated the development of diabetic nephropathy with elevations in urine albumin excretion, glomerular and renal hypertrophy, and mesangial matrix expansion. Increased glomerular lipid and apolipoprotein B accumulation was found in diabetic mice that consumed the 0.12% cholesterol diet compared with other groups. However, diabetic mice that changed from the high-cholesterol diet to the 0% cholesterol diet for the last 10 weeks had lower urine albumin excretion and mesangial matrix expansion compared with mice that consumed the 0.12% cholesterol diet throughout. This suggests that hyperlipidemia causes continuous renal injury, and that lowering cholesterol levels by dietary means can improve renal function in diabetic LDLR(-/-) mice.
高脂血症是糖尿病肾病发展和进展的一个危险因素。然而，降低血脂是否能预防疾病进展尚不清楚。本研究的目的是确定降低高胆固醇血症是否能限制糖尿病肾病的进展。给予糖尿病和非糖尿病 LDL 受体缺陷（LDLR(-/-)）小鼠含 0%或 0.12%胆固醇的饮食 36 周。每组各有一只糖尿病和非糖尿病小鼠先给予高胆固醇饮食 26 周，然后改为含 0%胆固醇饮食 10 周。高胆固醇饮食加重了糖尿病肾病的发展，表现为尿白蛋白排泄增加、肾小球和肾脏肥大以及系膜基质扩张。与其他组相比，给予 0.12%胆固醇饮食的糖尿病小鼠肾小球脂质和载脂蛋白 B 蓄积增加。然而，在最后 10 周从高胆固醇饮食改为 0%胆固醇饮食的糖尿病小鼠的尿白蛋白排泄和系膜基质扩张均低于持续给予 0.12%胆固醇饮食的小鼠。这表明高脂血症导致持续的肾脏损伤，通过饮食降低胆固醇水平可改善糖尿病 LDLR(-/-)小鼠的肾功能。
