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Fluvastatin prevents renal injury and expression of lactin-like exidized low-density lipoprotein receptor-1 in rabbits with hypercholesterolemia

查看全文 作　　者：YUYong-[1]hui;[2]WANGYi;[2]DONGBo;SUNShu-[2]zhen;[2]CHENYao;MENGXiao-[2]hui;LIUZhong-[2]zhi 高影响力作者 机构地区：[1]DepartmentofPediatrics,ShandongProvincialHospital,ShandongUniversity,Jinan250021,China;[2]DepartmentofPediatrics,ShandongProvincialHospital,ShandongUniversity,Jinan250021,China高影响力机构 出　　处：《Chinese Medical Journal》索引2005年第8期,共6页高影响力期刊 基　　金：ThisstudywassupportedbyagrantfromtheNationalNaturalScienceFoundationofChina(No 30371496) 摘　　要：Background Lipid abnormalities are often complicated by renal dysfunction. 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) are the first-line choice for lowering cholesterol levels. The present study was designed to investigate whether statins could prevent and invert the development of renal injury in cholesterol-fed rabbits and to find the possible mechanism of their effects by detecting gene and protein expression of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) in the renal artery.Methods Twenty-four male New Zealand white rabbits were divided into three groups: (1) control group, regular granules chow; (2) HC-diet group, granules chow with 1% cholesterol and 5% lard oil; and (3) fluvastatin group, 1% cholesterol and 5% lard oil diet plus fluvastatin (10 mg·kg -1 ·d -1 ) . After 16 weeks, serum total cholesterol (TC), low-density lipoprotein(LDL) and creatinine (Cr) levels were measured. Renal hemodynamics and function, mainly including glomerular filtration rate (GFR) in vivo were quantified using 99m Tc-DTPA single photon emission computed tomograph ( 99m Tc-DTPA SPECT). The thickness of the renal artery intima was quantitated in HE-stained segments by histomorphometry. Gene expression of LOX-1 in the renal artery was examined by semi-quantitative RT-PCR and its protein expression was evaluated by immunohistochemistry.Results High cholesterol diet induced hypercholesterolemia (HC) complicated by renal dysfunction with increased levels of serum lipid and Cr, decreased GFR and delayed excretion and extensively thickened renal arterial intima in the HC-diet group. Rabbits in the control group showed a minimal LOX-1 expression (mRNA and protein) in the endothelium and neointima of the renal artery. Intimal proliferation of the renal artery in the HC-diet group was associated with a marked increase of LOX-1 expression (protein and mRNA). Treatment with fluvastatin improved renal function, attenuated intimal proliferation of the renal artery and markedly decreased the enhanced LOX-1 expression in the endothelium and neointima of the renal artery in rabbits. Conclusions Fuvastatin treatment could prevent the development of renal injury in patients with HC and early atherosclerosis (AS). This beneficial effect might be mediated by its pleiotropic effects including a decrease in total cholesterol exposure level and prevention of LOX-1 expression in atherosclerotic arteries. 关 键 词：降脂静 药物预防 肾损伤 内酰亚胺 低密度脂蛋白受体-1 血胆脂醇过多症
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