Kim Hyun Ju, Vaziri Nosratola D
Division of Nephrology and Hypertension, University of California, Irvine, CA 92868, USA.
Am J Nephrol. 2009;29(6):607-14. doi: 10.1159/000193631. Epub 2009 Jan 16.
Accumulation of lipid in the kidney has been shown to promote renal disease. Heavy glomerular proteinuria (nephrotic syndrome) is associated with hyperlipidemia, lipiduria, and progressive kidney disease. Glomerular and tubular epithelial cells in the nephrotic kidney are exposed to large quantities of lipids bound to the filtered proteins whose uptake can raise cellular lipids. Cellular lipid homeostasis is regulated by the influx, synthesis and efflux of lipids.
We studied the expression of factors involved in lipid metabolism in the kidneys of nephrotic and control rats.
The nephrotic rats showed heavy proteinuria, hypercholesterolemia, increased kidney tissue cholesterol, marked activation (nuclear translocation) of SREBP-2 (master regulator of cholesterol synthesis), significant upregulations of CD36 and SRA-1 (key receptors for uptake of fatty acids and oxidized LDL) and ACAT1 (enzyme catalyzing intracellular esterification, hence trapping of cholesterol), but no significant change in either ABCA1 (mediator of cholesterol/phospholipid efflux) or its regulator, liver X receptor.
Proteinuria results in accumulation of cholesterol in the kidney. This is associated with upregulation of SRA-1, CD36 and ACAT1 and activation of SREBP-2 which can collectively raise tissue cholesterol and promote renal injury by facilitating the influx, synthesis and retention of cholesterol in the nephrotic kidney.
肾脏中脂质的积累已被证明会促进肾脏疾病。重度肾小球蛋白尿（肾病综合征）与高脂血症、脂尿症和进行性肾脏疾病相关。肾病肾脏中的肾小球和肾小管上皮细胞会接触到大量与滤过蛋白结合的脂质，这些脂质的摄取会增加细胞内脂质。细胞脂质稳态由脂质的流入、合成和流出调节。
我们研究了肾病大鼠和对照大鼠肾脏中参与脂质代谢的因子的表达。
肾病大鼠表现出重度蛋白尿、高胆固醇血症、肾脏组织胆固醇增加、SREBP - 2（胆固醇合成的主要调节因子）显著激活（核转位）、CD36和SRA - 1（脂肪酸和氧化低密度脂蛋白摄取的关键受体）以及ACAT1（催化细胞内酯化反应，从而捕获胆固醇的酶）显著上调，但ABCA1（胆固醇/磷脂流出的介质）及其调节因子肝脏X受体均无显著变化。
蛋白尿导致肾脏中胆固醇积累。这与SRA - 1、CD36和ACAT1的上调以及SREBP - 2的激活有关，它们共同作用可通过促进肾病肾脏中胆固醇的流入、合成和潴留来提高组织胆固醇水平并促进肾脏损伤。
