Nakao Akihide, Nosaka Kazuo, Imaki Hiromi, Noiri Eisei, Toda Akiko, Doi Kento, Suzuki Yoshifumi, Fujita Toshiro, Kimura Satoshi
Department of Nephrology and Endocrinology, School of Medicine, University of Tokyo, Tokyo, Japan.
Kidney Blood Press Res. 2004;27(2):96-104. doi: 10.1159/000076621. Epub 2004 Feb 6.
BACKGROUND/AIM: Spontaneously hypercholesterolemic (SHC) rats develop hypercholesterolemia and focal glomerular sclerosis, and have been thought to be a model of lipid-induced glomerular injury. However, recent studies suggest that the hypercholesterolemia might be due to secondary mechanisms by massive proteinuria. The purpose of the present study was to determine in SHC rats the effects of a high cholesterol diet on serum lipid profiles and renal function/histology, and to examine whether or not the model of lipid-induced renal injury could be developed in a short period of the time. The effects of probucol were also studied.
SHC rats were fed a high cholesterol diet for 6 weeks (H) or with probucol (HP), while control SHC rats were fed normal rat chow (N) or with probucol (P). Lipid profile and renal function/histology were examined.
H and HP showed increased levels of urinary protein excretion and serum creatinine, as well as extremely high serum cholesterol levels, compared with N and P. HP tended to show reduced urinary protein excretion compared with H, but the difference was not statistically significant. H and HP presented histologically characteristic changes with numerous foam cells accumulated in the glomerular mesangial area, and showed glomerular sclerosis.
The data demonstrate that SHC rats have an intrinsically abnormal lipid metabolism, and that probucol does not exert obviously beneficial effects on renal function or lipid-lowering action. A lipid-induced renal injury model of rats was produced in 6 weeks.
背景/目的：自发性高胆固醇血症（SHC）大鼠会出现高胆固醇血症和局灶性肾小球硬化，一直被认为是脂质诱导的肾小球损伤模型。然而，最近的研究表明，高胆固醇血症可能是由大量蛋白尿的继发机制引起的。本研究的目的是确定在SHC大鼠中高胆固醇饮食对血脂谱和肾功能/组织学的影响，并检查是否能在短时间内建立脂质诱导的肾损伤模型。同时也研究了普罗布考的作用。
将SHC大鼠喂以高胆固醇饮食6周（H组）或普罗布考（HP组），而对照SHC大鼠喂以正常大鼠饲料（N组）或普罗布考（P组）。检测血脂谱和肾功能/组织学。
与N组和P组相比，H组和HP组尿蛋白排泄量和血清肌酐水平升高，血清胆固醇水平极高。与H组相比，HP组尿蛋白排泄量有降低趋势，但差异无统计学意义。H组和HP组在组织学上呈现特征性变化，肾小球系膜区有大量泡沫细胞积聚，并出现肾小球硬化。
数据表明，SHC大鼠存在内在的脂质代谢异常，普罗布考对肾功能或降脂作用无明显有益影响。6周内建立了大鼠脂质诱导的肾损伤模型。
