Combined use of metformin and atorvastatin attenuates atherosclerosis in rabbits fed a high-cholesterol diet.
Combined use of metformin and atorvastatin attenuates atherosclerosis in rabbits fed a high-cholesterol diet.
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联合使用二甲双胍和阿托伐他汀可减轻高胆固醇饮食兔子的动脉粥样硬化
DOI：
10.1038/s41598-017-02080-w
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发表时间：
2017-05-19
影响因子：
4.6
通讯作者：
Li XP
中科院分区：
文献类型：
--
作者：
Luo F;Guo Y;Ruan GY;Long JK;Zheng XL;Xia Q;Zhao SP;Peng DQ;Fang ZF;Li XP
他汀类药物被广泛用于降低心血管风险。不幸的是，尽管使用了高强度的他汀类药物，一些患者仍然会出现心血管事件。二甲双胍是一种抗糖尿病药物，据报道具有抗动脉粥样硬化的作用。因此，本实验旨在评估二甲双胍和阿托伐他汀联合使用是否能获得额外的益处。在饲喂高胆固醇饮食的兔子中，我们评估了联合治疗对动脉粥样硬化斑块、脂质谱、血糖水平、肝肾功能的影响。在体外研究了联合治疗对胆固醇外排及相关转运蛋白表达的影响。我们的研究结果表明，联合治疗比阿托伐他汀更显著地减少了动脉粥样硬化病变面积，而没有额外的降脂作用。联合治疗可显著提高大密度脂蛋白亚区百分比。静脉葡萄糖耐量试验显示，阿托伐他汀处理的家兔在大剂量注射葡萄糖后，时间依赖性葡萄糖水平曲线下面积增加，而二甲双胍处理完全逆转了这一趋势。在培养的巨噬细胞中，二甲双胍和阿托伐他汀联合治疗可促进胆固醇外排，上调atp结合盒转运蛋白A1和G1的表达。综上所述，我们的研究结果表明，阿托伐他汀/二甲双胍联合治疗可能通过增加巨噬细胞中的胆固醇外排而获得额外的抗动脉粥样硬化益处。
Statins are widely used to reduce cardiovascular risk. Unfortunately, some patients still experience cardiovascular events though prescribed with high-intensity statins. Metformin, an anti-diabetic drug, was reported to possess anti-atherosclerotic effects. Therefore, the experiments were designed to evaluate whether combined use of metformin and atorvastatin can achieve additional benefits. In rabbits fed a high-cholesterol diet, we evaluated the effects of the combination therapy on atherosclerotic plaques, lipid profiles, blood glucose levels, liver and kidney functions. Effects of combination therapy on cholesterol efflux and the expression of related transporters were studiedin vitro. Our results showed that the combination therapy induced a more significant decrease in atherosclerotic lesion area than atorvastatin without additional lipid-lowering effect. The combination therapy significantly increased the percentage of large high-density lipoprotein subfraction. The intravenous glucose tolerance test showed that atorvastatin-treated rabbits had an increased area under the curve for time-dependent glucose levels after a bolus injection of glucose, which was completely reversed by metformin treatment. In cultured macrophages, co-treatment with metformin and atorvastatin promoted cholesterol efflux and up-regulated expression of ATP-binding cassette transporters A1 and G1. Taken together, our results suggest that atorvastatin/metformin combination therapy may achieve additional anti-atherosclerotic benefits likely through increasing cholesterol efflux in macrophages.