二甲双胍通过调节AMPK/ERK通路改善动脉粥样硬化小鼠血管平滑肌细胞异常增殖和动脉粥样硬化

Metformin improves the abnormal proliferation of vascular smooth muscle cells and atherosclerosis in atherosclerotic mice by regulating AMPK/ERK pathway

目的 探讨二甲双胍对动脉粥样硬化小鼠血管平滑肌细胞异常增殖和动脉粥样硬化的影响和机制。方法 将C57/B6小鼠分为对照组、模型组、二甲双胍组。油红O染色、免疫荧光染色法检测各组小鼠主动脉动脉粥样斑块沉积面积比例以及主动脉组织中Ki67和α-SMA表达情况。CCK-8、划痕实验和Western blotting分析小鼠血管平滑肌细胞增殖、迁移能力以及单磷酸腺苷依赖的蛋白激酶(AMPK)、细胞外调节蛋白激酶(ERK)通路和细胞骨架蛋白Pdlim5的变化。结果 与模型组比较,二甲双胍组小鼠主动脉动脉粥样斑块沉积面积比例、Ki67和α-SMA阳性细胞数、血管平滑肌细胞增殖和迁移能力、ERK水平均降低,而AMPK、Pdlim5水平升高(P<0.05)。结论二甲双胍通过调节AMPK和ERK通路改善高脂饮食介导小鼠血管平滑肌细胞异常增殖和动脉粥样硬化。

Aim To investigate the effect and mechanism of metformin on the abnormal proliferation of vascular smooth muscle cells and atherosclerosis in atherosclerotic mice. Methods C57/B6 mice were divided into control group, model group and metformin group. Oil red O staining and immunofluorescence staining were used to detect the proportion of aortic atherosclerotic plaque deposition area, Ki67 and α-SMA expression. CCK-8, scratch test and Western blotting were used to analyze the proliferation and migration of mouse vascular smooth muscle cells, and the changes of adenosine monophosphate dependent protein kinase(AMPK), extracellular regulated protein kinase(ERK) pathway and cytoskeleton protein Pdlim5. Results Compared with model group, the proportion of aortic atherosclerotic plaque deposition, the number of positive cells of Ki67 and α-SMA, the proliferation and migration ability of vascular smooth muscle cells, and the ERK level decreased, while the AMPK and Pdlim5 levels increased(P<0.05). Conclusion Metformin improves the abnormal proliferation of vascular smooth muscle cells and atherosclerosis in mice induced by high-fat diet by regulating AMPK and ERK pathways.