瑞舒伐他汀作用于淋巴系统改善动脉粥样硬化

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. Western blotting showed that rosuvastatin increased the protein expression of SR-B1. Conclusion: Rosuvastatin can promote the proliferation, migration and tube formation of lymphatic endothelial cells. At the same time, SR-B1 expression on lymphatic endothelial cells is promoted, thus enhancing the lymphatic system mediated cholesterol reversal transport and playing the role of anti-atherosclerosis.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。.