Abstract: AIM: To study the effects of atorvastatin on the atherosclemtic (AS) lesion formation and expression of the hepatic ApoA-I and scavenger receptor-1 (SR-B1) in apolipoprotein E-deficient (ApoE^-/-) mice.METHODS: Thirty male ApoE^-/- mice were randomized into three groups: control group (group B, saline vehicle), atorvastatin low dose group (group C, 10 mg·kg^-1·d^-1) and high dose group (group D, 20 mg·kg^-1·d^-1).Ten male C57BL/6J mice as normal group (group A, saline vehicle) were treated with saline vehicle. At the end of twelve weeks of drug administration,all mice were sacrificed.The serum levels of total cholesterol (TC),triglyceride (TG) and high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C) were measured.Atherosclerotic plaque in the thoracic aorta was examined using Hematoxy-Eosin staining and oil red O staining. ApoA-I and SR-B1 were detected by Western blot. Real-time quantitative PCR was used to determine the ApoA-I and SR-B1 mRNA expressions in the liver.RESULTS: Significant hyperlipidemia and atherosclerotic plaque formation were detected in ApoE^-/- mice, compared with group A [TG: (2.93±0.18) mmol/L vs (0.59±0.09)mmol/L;TC:(21.78±2.03) mmol/L vs (2.13±0.24) mmol/L;HDL-C:(2.86±0.26) mmol/L vs (0.57±0.10) mmol/L;LDL-C:(18.92±1.87) mmol/L vs (1.54±0.21) mmol/L;P<0.01]. Treatment with atorvastatin decreased serum concentration of TC and LDL-C [TC group B:(21.78±2.03) mmol/L, group C:(11.79±0.98) mmol/L,group D(10.07±1.03) mmol/L;LDL-C group B:(18.92±1.87) mmol/L,group C:(8.76±1.15)mmol/L,group D:(7.91±0.77) mmol/L;P<0.01], and reduced area of the atherosclerotic plaque compared with ApoE^-/- control mice [group B:(23.12±3.46)×10⁴ μm²,group C:(11.42±1.25)×10⁴ μm²,group D:(7.34±1.03)×10⁴ μm²,P<0.01]. Atorvastatin up-regulated the expression of ApoA-I and SR-B1 compared with ApoE^-/- control mice (ApoA-I group B:1.08±0.10,group C:1.36±0.11,group D:1.78±0.14;SR-B1 group B:0.72±0.07,group C:1.46±0.14,group D:1.50±0.21, P<0.01).CONCLUSION: Atorvastatin impeded the progression of atherosclerosis in ApoE^-/- mice possibly through improvement of lipid metabolism and up-regulation of ApoA-I and SR-B1.

Key words: Atorvastatin, Apolipoprotein E-deficient mouse, ApoA-I, SR-B1