2024 年第 6 期 第 0 卷

秋水仙碱对高脂饮食诱导的载脂蛋白E基因敲除小鼠动脉粥样硬化的影响

Effect of colchicine on atherosclerosis induced by high-fat diet in apolipoprotein E gene knockout mice

作者：段小春1严研2祖晓天1李雅敏1杨波3李南2

英文作者：Duan Xiaochun1 Yan Yan2 Zu Xiaotian1 Li Yamin1 Yang Bo3 Li Nan2

单位：1首都医科大学附属北京安贞医院急诊危重症中心，北京100029；2首都医科大学附属北京安贞医院心内科冠心病中心，北京100029；3首都医科大学附属北京安贞医院心脏外科，北京100029

英文单位：1Emergency and Critical Care Center Beijing Anzhen Hospital Capital Medical University Beijing 100029 China; 2Center for Coronary Artery Disease Department of Cardiology Beijing Anzhen Hospital Capital Medical University Beijing 100029 China; 3Department of Cardiac Surgery Beijing Anzhen Hospital Capital Medical University Beijing 100029 China

关键词：动脉粥样硬化；秋水仙碱；高脂饮食；凋亡

英文关键词：Atherosclerosis;Colchicine;High-fatdiet;Apoptosis

• 摘要：

• 目的 探讨秋水仙碱对高脂饮食诱导的载脂蛋白E基因敲除（ApoE-/-）小鼠动脉粥样硬化的影响。方法 选取12只C57BL/6J野生型小鼠作为对照组；24只ApoE-/-小鼠完全随机分为模型组和秋水仙碱组、每组12只。对照组给予普通饲料喂养；模型组、秋水仙碱组给予高脂饲料喂养建立动脉粥样硬化模型，秋水仙碱组同时给予秋水仙碱2 mg/（kg·d）灌胃，持续8周。留取小鼠血液和主动脉组织标本，检测各组血脂及C反应蛋白水平，染色观察小鼠主动脉病理变化，比较各组动脉粥样硬化斑块核帽比及易损指数。结果 干预后模型组、秋水仙碱组总胆固醇、甘油三酯、低密度脂蛋白胆固醇、C反应蛋白均高于对照组但秋水仙碱组低于模型组，高密度脂蛋白胆固醇均低于对照组但秋水仙碱组高于模型组（均P<0.05）。秋水仙碱组小鼠主动脉内皮细胞凋亡数量、胶原纤维含量、主动脉组织CD68和α-平滑肌肌动蛋白阳性表达量均显著低于模型组（均P<0.05）。秋水仙碱组小鼠动脉粥样硬化斑块核帽比和易损指数显著低于模型组［（3.24±0.49）比（9.54±1.49）、（2.84±0.39）比（8.64±1.29）］（均P<0.05）。结论 秋水仙碱可显著减轻高脂饮食诱导的ApoE-/-小鼠主动脉粥样硬化。

• Objective To investigate the effect of colchicine on atherosclerosis induced by high-fat diet in apolipoprotein E gene knockout(ApoE-/-) mice. Methods Twelve C57BL/6J wild-type mice were selected as the control group, 24 ApoE-/- mice were completely randomized into model group and colchicine group, with 12 mice in each group. The control group was fed with regular feed; the model group and colchicine group were fed with high-fat diet to establish atherosclerosis model, at the same time colchicine group was also given colchicine 2 mg/(kg·d) by gavage for 8 weeks. The blood and aortic tissue samples were collected to detect the levels of blood lipids and C-reactive protein in each group. The pathological changes of aorta were observed by staining. The nuclear/cap ratio and vulnerability index of atherosclerotic plaques were compared among the groups. Results After intervention, the total cholesterol, triglycerides, low-density lipoprotein cholesterol, and C-reactive protein in the model group and colchicine group were higher than those in the control group, but those in the colchicine group were lower than those in the model group, and the high-density lipoprotein cholesterol was lower than that in the control group, but those in the colchicine group were higher than those in the model group(all P<0.05). The number of apoptotic endothelial cells, collagen fiber content, and CD68, α-smooth muscle actin positive expression in the aortic tissue of mice in the colchicine group were significantly lower than those in the model group (all P<0.05). The ratio of nucleus to cap and vulnerability index of atherosclerotic plaque in colchicine group were significantly lower than those in model group ［(3.24±0.49) vs (9.54±1.49), (2.84±0.39) vs (8.64±1.29)］(both P<0.05). Conclusion Colchicine can significantly reduce aortic atherosclerotic in ApoE-/- mice induced by high-fat diet.