瑞舒伐他汀作用于淋巴系统改善动脉粥样硬化  

Rosuvastatin acts on the lymphatic system to improve atherosclerosis

作　　者：宋子琪 宋俊贤[1] 崔淯夏[1] 李素芳[1] 陈红[1] Song Ziqi;Song Junxian;Cui Yuxia;Li Sufang;Chen Hong(Beijing Key Laboratory of Early Warning and Intervention of Acute Myocardial Infarction,Cardiovascular Translational Medicine Research Center,Department of Cardiovascular Medicine,Peking University People′s Hospital,Beijing 100044,China)

机构地区：[1]北京大学人民医院心血管内科、心血管转化医学研究中心、急性心肌梗死早期预警和干预北京市重点实验室,北京100044

出　　处：《中华心血管病杂志》2023年第3期288-295,共8页Chinese Journal of Cardiology

基　　金：国家自然科学基金(81970301);北京市自然科学基金(7202218)。

摘　　要：目的探讨瑞舒伐他汀是否作用于淋巴系统,影响淋巴系统介导的胆固醇逆转运发挥抗动脉粥样硬化作用。方法使用48只高脂饮食饲养载脂蛋白E-/-小鼠构建动脉粥样硬化模型。随机分为4组,每组12只,分别予瑞舒伐他汀、血管内皮生长因子-C(VEGF-C)、瑞舒伐他汀+VEGF-C抑制剂作为实验组,对照组无干预措施。8周后检测小鼠主动脉斑块面积,淋巴液内高密度脂蛋白胆固醇(HDL-C)含量、腘窝淋巴管引流外周Evans蓝的功能、淋巴系统转运外周细胞膜红色荧光探针标记高密度脂蛋白(HDL)的能力。随后分别检测不同浓度瑞舒伐他汀对淋巴内皮细胞增殖、迁移、成管功能的影响和对淋巴内皮细胞上B类1型清道夫受体(scavenger receptor class B type 1,SR-B1)表达的影响。结果与对照组相比,瑞舒伐他汀和VEGF-C可以减小主动脉动脉粥样硬化斑块面积(P<0.05)。在瑞舒伐他汀他汀基础上加用VEGF-C抑制剂,主动脉内斑块面积增加(P<0.05)。与对照组相比,瑞舒伐他汀可以增加小鼠淋巴液内HDL-C含量(P<0.05),增强淋巴管引流功能,增强淋巴系统转运组织液中HDL的能力。与对照组相比,VEGF-C增加小鼠淋巴液内HDL-C的含量(P<0.01)、增强腘窝淋巴管引流功能、增强淋巴系统转运HDL的能力。在瑞舒伐他汀基础上加用VEGF-C抑制剂,淋巴液中HDL-C含量减少、腘窝淋巴管出现引流中断,淋巴系统转运HDL的能力降低。免疫印迹试验结果显示,瑞舒伐他汀可以增加SR-B1的蛋白表达。结论瑞舒伐他汀可促进淋巴内皮细胞的增殖、迁移和成管;同时促进淋巴内皮细胞上SR-B1的表达,从而增强淋巴系统介导的胆固醇逆转运,发挥抗动脉粥样硬化作用。Objective To investigate whether rosuvastatin acts on lymphatic system and influences lymphatic system-mediated reverse cholesterol transport to play an anti-atherosclerosis role.Methods Forty-eight apolipoprotein E-/-mice fed a high fat diet were used to construct the atherosclerosis model.They were randomly divided into 4 groups with 12 rats in each group.They were treated with rosuvastatin,vascular endothelial growth factor-C(VEGF-C)and rosuvastatin+VEGF-C inhibitors as experimental group,and no intervention measures were given in control group.After 8 weeks,aortic plaque area,high density lipoprotein cholesterol(HDL-C)content in lymph fluid,the function of popliteal lymphatic drainage of peripheral Evans blue,and the ability of lymphatic system to transport peripheral cell membrane red fluorescent probes to label high-density lipoprotein(HDL)were detected.Subsequently,the effects of rosuvastatin on proliferation,migration and tubular function of lymphoendothelial cells and the expression of scavenger receptor class B type 1(SR-B1)on lymphoendothelial cells at different concentrations were detected.Results Compared with the control group,Rosuvastatin and VEGF-C could reduce the area of aortic atherosclerotic plaque(P<0.05).In addition to rosuvastatin plus VEGF-C inhibitor,the intra-aortic plaque area increased(P<0.05).Compared with the control group,Rosuvastatin could increase the content of HDL-C in lymphatic fluid(P<0.05),enhance the drainage function of lymphatic vessels,and enhance the capacity of HDL in the transport tissue fluid of lymphatic system.Compared with the control group,VEGF-C increased the content of HDL-C in mouse lymph fluid(P<0.01),enhanced the drainage function of popliteal lymphatic canal,and enhanced the ability of lymphatic system to transport HDL.With the addition of VEGF-C inhibitor on the basis of rosuvastatin,the content of HDL-C in lymph fluid was reduced,the drainage of popliteal lymphatic canal was interrupted,and the ability of lymphatic system to transport HDL was reduced.Weste

关 键 词：动脉粥样硬化 胆固醇逆转运 淋巴系统 瑞舒伐他汀 

分 类 号：R543.5[医药卫生—心血管疾病]