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Title:: Effects of combined rosiglitazone and atorvastatin on aortic atherosclerotic area and tissue factor synthesis in atherosclerotic rabbits

作者:: 吴旭斌¹; 周胜华²; 刘伶¹; 黄宗燕¹; 吴宁¹; 林英忠¹; 1.广西壮族自治区人民医院心内科,广西南宁 530021; 2.中南大学湘雅二院心血管内科，湖南长沙 410011

Author(s):: WU Xu-bin¹; ZHOU Sheng-hua²; LIU Ling¹; HUANG Zong-yan¹; WU Ning¹; LIN Ying-zhong¹; 1.Department of Cardiology, Peoples Hospital of Guangxi Zhuangzu Autonomous Region, Nanning 530021, Guangxi, China; 2.Department of Cardiology, Second Xiangya Hospital of Central South University, Changsha 410011, Hunan, China

关键词:: 罗格列酮; 阿托伐他汀; 动脉粥样硬化; 组织因子

Keywords:: rosiglitazone; atorvastatin; atherosclerosis; tissue factor

分类号:: R541.4

DOI:: -

文献标识码:: A

摘要:: 目的: 探讨罗格列酮和阿托伐他汀单独或联合应用对动脉粥样硬化兔主动脉斑块面积及外周血单核细胞合成组织因子（TF）的影响。方法: 30只雄性新西兰大白兔随机分成普通饮食喂养（对照组，n=6）和高胆固醇饮食喂养（高胆固醇饮食组，n=24）。8周后，高胆固醇饮食组兔随机加喂淀粉（淀粉组，n=6）或阿托伐他汀5 mg/（kg·d）（阿托伐他汀组，n=6）或罗格列酮3 mg/（kg·d）（罗格列酮组，n=6）或罗格列酮3 mg/（kg·d）联合阿托伐他汀5 mg/（kg·d）（联合组，n=6）4周。各组兔共喂养12周后，取兔主动脉测定内膜斑块面积，同时分离外周血单核细胞培养24 h，采用酶联免疫吸附测定法检测单核细胞细胞TF水平，用逆转录聚合酶链反应（RT-PCR）测定TF mRNA的表达。结果: 高胆固醇饮食各组兔主动脉粥样硬化形成，与对照组相比，高胆固醇饮食各组兔外周血单核细胞合成TF水平升高（均P<0.01）；与淀粉组相比，阿托伐他汀和罗格列酮体内干预都能降低动脉粥样硬化兔主动脉斑块面积百分数、外周血单核细胞合成TF水平（均P<0.01）；二者联合干预，能更显著地降低主动脉斑块面积、外周血单核细胞合成TF（均P<0.01）；兔主动脉斑块面积，与外周血单核细胞合成TF蛋白和TF mRNA水平呈显著正相关（均P<0.01）。结论: 阿托伐他汀和罗格列酮具有一定的抗动脉粥样硬化作用，二者联合应用具有协同抗动脉粥样硬化作用。抑制单核细胞合成TF可能是它们的作用机制之一。

Abstract:: AIM: To investigate the effects of a single administration of rosiglitazone or atorvastatin and combined administration of both on aortic atherosclerotic area and tissue factor (TF) synthesis in peripheral blood monocytes from atherosclerotic rabbits. METHODS: Thirty male New Zealand rabbits were randomly divided into normal diet group (n=6) and high-cholesterol diet group (1% cholesterol diet, n=24). After 8 weeks, atherosclerotic rabbits were randomly fed with starch (starch group, n=6), rosiglitazone (rosiglitazone group, n=6), or atorvastatin (atorvastatin group, n=6), or both rosiglitazone and atorvastatin (combination group, n=6). Four weeks later, all rabbits were killed. Monocytes were isolated from peripheral blood monocytes and then cultured for 24 h. TF synthesis was assessed by reverse transcriptase polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). Atherosclerotic lesions were measured by an experienced pathologist under Beihang Pathology Imaging Analysis System in aortas from atherosclerotic rabbits. RESULTS: Compared with those in the normal diet group, levels of TF antigen and mRNA in monocytes from high-cholesterol diet groups were elevated. Compared with starch, rosiglitazone and atorvastatin decreased the area of atherosclerotic lesions and reduced the levels of TF antigen and mRNA in peripheral blood monocytes from atherosclerotic rabbits. Furthermore, compared with the group of rosiglitazone or atorvastatin, the group of rosiglitazone plus atorvastain achieved a more significant reduction (P<0.01). The area of atherosclerotic lesions were significantly associated with the concentrations of TF antigen and mRNA in monocytes (P<0.01), respectively. CONCLUSION: Both rosiglitazone and atorvastatin assuage atherosclerosis through suppressing TF synthesis in peripheral blood monocytes from atherosclerotic rabbits. Synergistic administration of rosiglitazone and atorvastatin exerts better anti-atheromatous effects.

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罗格列酮联合阿托伐他汀对动脉粥样硬化兔主动脉斑块面积和组织因子的影响

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

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