阿托伐他汀对高胆固醇血症兔主动脉环氧合酶2的影响  

Influence and Significance of Atorvastatin on Cyclooxygenase-2 in Aortas From Hypercholesterolemic Rabbits

作　　者：邓平[1] 赵水平[1] 戴海鹰[1] 黄红光[1] 洪绍彩[1] 吴智鸿[1] 

机构地区：[1]中南大学湘雅二医院心内科

出　　处：《中国动脉硬化杂志》2006年第2期132-136,共5页Chinese Journal of Arteriosclerosis

摘　　要：目的检测环氧合酶2在高胆固醇血症兔主动脉粥样硬化中的表达,探讨阿托伐他汀对环氧合酶2表达的影响及其意义。方法选取健康雄性新西兰兔24只,随机分为正常饮食组(n=8)和高胆固醇饮食组(n=16),喂养8周后,将后者随机分为高胆固醇血症组(n=8)和阿托伐他汀组[2.5 mg/(kg.d),n=8],继续喂养6周后,取各组兔主动脉,行动脉粥样硬化病变面积测定,采用逆转录聚合酶链反应检测主动脉环氧合酶2 mRNA的表达,酶联免疫吸附法测定血清白细胞介素6水平,免疫组织化学法测定主动脉粥样硬化斑块中环氧合酶2和基质金属蛋白酶9的表达。结果高胆固醇饮食兔经阿托伐他汀干预6周后,动脉粥样硬化斑块面积较高胆固醇血症组显著缩小(43.0%±12.5%比83.0%±11.6%,P<0.05)。高胆固醇饮食兔主动脉环氧合酶2 mRNA表达较正常饮食兔明显增强(1.03±0.09比0.09±0.01,P<0.05),阿托伐他汀干预后明显下降(0.57±0.10,P<0.05),且主动脉环氧合酶2 mRNA表达与斑块面积和血清白细胞介素6水平均呈正相关(r分别为0.803和0.795,P均<0.05)。高胆固醇血症组14周时主动脉粥样硬化斑块中环氧合酶2蛋白表达明显增强,而阿托伐他汀组显著性降低(62.4%±8.5%比34.3%±8.8%,P<0.05),且环氧合酶2蛋白表达与基质金属蛋白酶9的蛋白表达呈正相关(r=0.887,P<0.05)。结论环氧合酶2在动脉粥样硬化的发生和发展中可能起重要的促进作用,阿托伐他汀可能通过降低高胆固醇血症兔主动脉及其粥样斑块中环氧合酶2的表达,抑制基质金属蛋白酶9和白细胞介素6的分泌,从而发挥降脂以外的抗炎症作用。Aim To study the effect of atorvastatin on the expression of eyelooxygenase-2 （ COX-2 ） and other proinflammatory moleeules in a rabbit model of atherosclerosis and to further explore the potential mechanism of atorvastatin in antl-atberoselerostie inflammation beyond the lowing lipid. Methods Twenty-four male New Zealand rabbits （3 months old）were fed with normal diet （ n = 8） and high-cholesterol diet （ n = 16） respectively for 8 weeks, and then the high-cholesterol diet rabbits were assigned to receive either atorvastatin 2.5 mg/（kg·d） （ n = 8）or starch （ n = 8）. 6 weeks later, aortas were removed under deep anesthetization. The femoral arteries were removed to determine COX-2 mRNA by reverse transcription-polymerase ehain reaetion and the level of COX-2 and matrix metalloproteinase-9 （MMP-9） protein by immunohistochemistry. Atherosclerotie lesions were measured by experienced pathologist under Beihang Pathology Imaging Analysis System in aortas from hypereholesterolemie rabbits. Plasma interleukin-6 （IL-6） levels were measured by enzyme linked immunosorbent assay （ELISA）. Resuits Compared with plaeebo-treated group,atheroselerotie area was redueed in atorvastatin-treated group （43.0% ±12.5% vs 83.0% ± 11.6%, P 〈 0.05）. COX-2 mRNA expression in aortas from hypereholesterolemie rabbits were signifieandy increased compared with those from normal rabbits, and signifieandy reduced by the treatment of atorvastatin （1.03 ± 0.09 vs 0.57 ± 0.10, P 〈 0.05）, and the levels of COX-2 mRNA expression were related to both atheroselerotie area and plasma IL-6 levels （ r = 0. 803 and 0. 795, both P 〈 0.05 ）. Expression of COX-2 protein in atheroselerostie plaques were significandy increased and reduced by the treatment of atorvastatin （62.4% ±8.5% vs 34.3% ± 8.8%, P 〈 0.05）, and the levels of COX-2 were related to the levels of MMP-9 in atheroselerostie plaques （ r = 0. 815, P 〈 0. 05 ）. Conclusion In hypercholesterolemie rabbits, atorvastatin can de

关 键 词：药理学 阿托伐他汀对动脉粥样硬化炎症的影响 逆转录聚合酶链反应 环氧合酶2 阿托伐他汀 高胆固醇血症 动脉粥样硬化 

分 类 号：R96[医药卫生—药理学]