Impact of different lipid lowering scheme on the liver and kidney function and endothelial function in arteriosclerosis rats model

XU Yan-ling; ZHANG Jing; ZHOU Lin

doi:10.3760/cma.j.issn.1673-4777.2013.04.004

Abstract：Objective To investigate vascular endothelial function,liver function and renal function of mixed hyperlipidemia rats treated by different ways including high doses of simvastatin and small doses of simvastatin combined with ezetimibe.Methods Forty-two healthy Wistar 6-month-old male rats were randomly divided into five groups,including normal control group (n =8),hyperlipidemia control group (n =10),low dose of simvastatin [10 mg/(kg · d)] group (n =8),high dose of simvastatin [20 mg/(kg · d)] group (n =8),simvastatin [10 mg/(kg · d)] combined with ezetimibe [5 mg/(kg · d)] group (n =8).Levels of total cholesterol (TC),lowdensity lipoprotein cholesterol (LDL-C),high-density lipoprotein cholesterol(HDL-C),triglycerides (TG),alanine aminotransferase (ALT),aspartate aminotransferase (AST),serum creatinine (Scr),urea nitrogen (BUN),uric acid,urine protein,urine creatinine (Ucr),serum creatinine clearance rate (Ccr),C-reactive protein (CRP),soluble thrombomodulin regulatory proteins (sTM) and soluble intercellular adhesion molecule-1 (sICAM-1) and urinary protein were tested in all groups.Renal index was also calculated.Results ① Compared with hyperlipidemia control group,levels of TC,IDL-C,TG,ALT,AST,BUN,uric acid,urine protein,CRP,sTM and sICAM-1 in all the therapeutic groups were significantly lower (P ＜0.01).But HDL-C and Ccr levels were significantly higher.Renal function were improved and levels of sTM and slCAM-1 were significantly lower (P ＜ 0.01) in high dose of simvastatin [20 mg/(kg· d)] group.Liver function were improved and limpid-lowering were better in simvastatin [10 mg/(kg · d)] combined with ezetimibe [5 mg/(kg · d)] group.②Small size of glomerular and mesangial cell proliferation relief were seen in the therapeutic groups with light microscope.And high dose of simvastatin group had better results.Conclusions ①Compared with simvastatin combined with ezetimibe group,high dose of simvastatin treatment has lower levels of BUN,uric acid,urine protein,sTM and sICAM-1,can reduce renal index,increase Ccr and HDL-C levels,improve glomerular morphology and improve renal function and vascular endothelial function.②Compared with high-dose simvastatin group,small doses of simvastatin and ezetimibe treatment can significantly reduce TC,LDL-C and CRP levels,don't affect serum transaminase levels,and reduce lipid effectively but not increase damage of liver function.