阿托伐他汀对ApoE-/-小鼠载脂蛋白A-I和B族1型清道夫受体的影响

中国临床药理学与治疗学 ›› 2013, Vol. 18 ›› Issue (11): 1233-1237.

阿托伐他汀对ApoE^-/-小鼠载脂蛋白A-I和B族1型清道夫受体的影响

丁洁卫¹, 王建平²

¹绍兴市人民医院,浙江大学绍兴医院临床药学科,绍兴 312000,浙江;
²浙江省中医院药剂科,杭州 310006,浙江

收稿日期:2012-10-10 修回日期:2013-03-20 出版日期:2013-11-26 发布日期:2013-11-22
通讯作者: 王建平,男,硕士,主任药师,主要从事临床药理研究。Tel: 0571-87068001 E-mail: jim917@163.com
作者简介:丁洁卫,女,主任药师,主要从事临床药学研究。Tel: 0575-88228768 E-mail: sxdjw888@163.com

Effects of atorvastatin on ApoA-I and SR-B1 in ApoE-deficient mice

DING Jie-wei¹, WANG Jian-ping²

¹Department of Pharmacy,Shaoxing People's Hospital;Shaoxing Hospital of Zhejiang University,Shaoxing 312000, Zhejiang,China;
²Research Center for Clinical Pharmacy, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang ,China

Received:2012-10-10 Revised:2013-03-20 Online:2013-11-26 Published:2013-11-22

摘要/Abstract

摘要： 目的: 观察阿托伐他汀对载脂蛋白E基因敲除(ApoE^-/-)小鼠动脉粥样硬化(AS)病变形成及载脂蛋白A-I(ApoA-I)和B族1型清道夫受体(SR-B1)表达水平的影响,探讨阿托伐他汀抑制AS病变形成的可能机制。方法: C57BL/6J小鼠 10只作为正常对照组常规饲养(A组),ApoE^-/-小鼠30只高脂饮食饲养,随机分为ApoE^-/-高脂模型组(B组)、阿托伐他汀小剂量组(10 mg·kg^-1·d^-1,C组)和阿托伐他汀大剂量组(20 mg·kg^-1·d^-1,D组)。给予生理盐水或药物干预12周后,测定小鼠血脂水平,HE染色和油红O染色观察各组小鼠胸主动脉粥样斑块的病理改变,采用Western blot法测定肝组织ApoA-I和SR-B1表达水平,实时定量PCR法测定肝组织ApoA-I和SR-B1 mRNA表达水平。结果: 与A组相比,B组血清TG、TC、低密度脂蛋白胆固醇(LDL-C)和高密度脂蛋白胆固醇(HDL-C)明显升高[分别为(2.93±0.18) mmol/L vs (0.59±0.09) mmol/L;(21.78±2.03) mmol/L vs (2.13±0.24) mmol/L;(2.86±0.26) mmol/L vs (0.57±0.10) mmol/L;(18.92±1.87) mmol/L vs (1.54±0.21) mmol/L;P<0.01]。与B组相比,C组和D组TC、LDL-C明显下降 [TC B组:(21.78±2.03)mmol/L,C组:(11.79±0.98) mmol/L,D组:(10.07±1.03) mmol/L;LDL-C B组:(18.92±1.87) mmol/L,C组:(8.76±1.15) mmol/L,D组:(7.91±0.77) mmol/L;P<0.01]。胸主动脉粥样斑块面积明显减小[B组:(23.12±3.46)×10⁴ μm²,C组:(11.42±1.25)×10⁴ μm²,D组:(7.34±1.03)×10⁴ μm²,P<0.01];肝组织 ApoA-I和SR-B1表达水平明显上调(ApoA-I B组:1.08±0.10,C组:1.36±0.11,D组:1.78±0.14;SR-B1 B组:0.72±0.07,C组:1.46±0.14,D组:1.50±0.21, P<0.01)。结论: 阿托伐他汀可以通过降低ApoE^-/-小鼠胆固醇水平,上调ApoA-I和SR-B1表达,发挥抗动脉粥样硬化的作用。

关键词: 阿托伐他汀, ApoE^-/-小鼠, B族1型清道夫受体, 载脂蛋白A-I

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

中图分类号:

R965.2

丁洁卫, 王建平. 阿托伐他汀对ApoE^-/-小鼠载脂蛋白A-I和B族1型清道夫受体的影响[J]. 中国临床药理学与治疗学, 2013, 18(11): 1233-1237.

DING Jie-wei¹, WANG Jian-ping². Effects of atorvastatin on ApoA-I and SR-B1 in ApoE-deficient mice[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2013, 18(11): 1233-1237.

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