2022 年第 6 期 第 17 卷

匹伐他汀对稳定型冠心病患者巨噬细胞胆固醇外流功能的影响及机制研究

Effect and mechanism of pitavastatin on cholesterol efflux function of macrophages in patients with stable coronary atherosclerotic heart disease

作者：王会娟王继红赵兴山刘巍

英文作者：Wang Huijuan Wang Jihong Zhao Xingshan Liu Wei

单位：北京积水潭医院心内科，北京102208

英文单位：Department of Cardiology Beijing Jishuitan Hospital Beijing 102208 China

关键词：稳定型冠心病（冠状动脉粥样硬化性心脏病）；高密度脂蛋白；胆固醇外流；三磷酸腺苷结合盒转运蛋白A1；三磷酸腺苷结合盒亚家族G1抗体

英文关键词：Stablecoronaryatheroscleroticheartdisease;High-densitylipoprotein;Cholesterolefflux;Adenosinetriphosphate-bindingcassettetransporterA-1;Adenosinetriphosphate-bindingcassettetrasnsporterG-1

• 摘要：

• 目的 研究匹伐他汀对稳定型冠心病（冠状动脉粥样硬化性心脏病）患者单核细胞来源的巨噬细胞的胆固醇外流功能的影响及其机制。方法 选取2019年1月至2021年1月北京积水潭医院心内门诊及病房的合并脂代谢异常的稳定型冠心病患者60例，采用简单随机化分组的方法分为匹伐他汀组和阿托伐他汀组（各30例），分别予以匹伐他汀2～4 mg/d或阿托伐他汀10～20 mg/d，治疗6个月。分别于治疗前及治疗6个月后抽取外周静脉血，测定血脂水平。分离单核细胞进行巨噬化培养，实时定量聚合酶链反应法测定三磷酸腺苷结合盒转运蛋白A1（ABCA1）及三磷酸腺苷结合盒亚家族G1抗体(ABCG1)的mRNA表达水平,蛋白质印迹法检测ABCA1及ABCG1的蛋白表达水平。以3H标记胆固醇分别测定经载脂蛋白A1及高密度脂蛋白（HDL）介导的胆固醇外流率变化。结果 治疗6个月后，匹伐他汀组高密度脂蛋白胆固醇（HDL-C）水平［（1.34±0.15）mmol/L比（1.21±0.18）mmol/L］，载脂蛋白A1和HDL介导的胆固醇外流率［（11.4±2.2）%比（8.6±1.7）%、（17.7±1.7）%比（12.8±1.6）%］，巨噬细胞中检测到ABCA1 及ABCG1 mRNA和蛋白表达水平均高于治疗前，差异均有统计学意义（均P＜0.05）。而阿托伐他汀组治疗6个月后，HDL-C水平，载脂蛋白A1和HDL介导的胆固醇外流率，巨噬细胞中检测到ABCA1及ABCG1 mRNA和蛋白表达水平与治疗前比较，差异均无统计学意义（均P＞0.05）。结论 匹伐他汀治疗合并脂代谢异常的稳定型冠心病患者，在升高HDL-C水平的同时，可使ABCA1及ABCG1的表达上调，从而显著改善HDL介导的胆固醇外流功能。

• Objective To study the effect and mechanism of pitavastatin on cholesterol efflux function of monocyte-derived macrophages in patients with stable coronary atherosclerotic heart disease. Methods Totally 60 patients with stable coronary atherosclerotic heart disease complicated with dyslipidemia in the intracardiac clinic and ward of Beijing Jishuitan Hospital from January 2019 to January 2021 were enrolled. Patients were randomly divided into pitavastatin group and atorvastatin group, with 30 cases in each group. They were treated with pitavastatin 2-4 mg/d or atorvastatin 10-20 mg/d for 6 months, respectively. Peripheral venous blood was taken before treatment and 6 months after treatment to measure the blood lipid level. Monocytes were isolated for macrophage culture. The mRNA expression levels of adenosine triphosphate-binding cassette transporter A-1(ABCA1) and adenosine triphosphate-binding cassette trasnsporter G-1(ABCG1) were measured by real-time quantitative polymerase chain reaction, and the protein expression levels of ABCA1 and ABCG1 were detected by western blotting. The changes of cholesterol efflux rate mediated by apolipoprotein A1 and high density lipoprotein (HDL) were measured by 3H labeled cholesterol. Results   After 6 months of treatment, the level of high-density lipoprotein cholesterol (HDL-C)［（1.34±0.15）mmol/L vs （1.21±0.18）mmol/L］, the cholesterol efflux rate mediated by apolipoprotein A1 and HDL［ （11.4±2.2）% vs （8.6±1.7）%, （17.7±1.7）% vs （12.8±1.6）%］, and the expression levels of ABCA1 and ABCG1 mRNA and protein in macrophages in pitavastatin group were significantly higher than those before treatment (all P＜0.05). After 6 months of treatment in atorvastatin group, there were no significant differences in HDL-C level, apolipoprotein A1 and HDL mediated cholesterol efflux rate, and ABCA1 and ABCG1 mRNA and protein expression in macrophages (all P＞0.05). Conclusions  For patients with stable coronary atherosclerotic heart disease complicated with dyslipidemia, pitavastatin can not only increase the level of HDL-C, but also up regulate the expression of ABCA1 and ABCG1, so as to significantly improve the cholesterol efflux function mediated by HDL.