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目的观察阿托伐他汀对肌细胞增强因子2A(MEF2A)基因突变型血管平滑肌细胞(VSMC)的作用。方法将人主动脉血管平滑肌细胞分为3组:①WT组,转染野生型(WT)MEF2A质粒;②△21组,转染21碱基缺失突变型(△21)MEF2A质粒;③阿托伐他汀组,转染MEF2A△21质粒,并在实验前向该组细胞培养基中加入阿托伐他汀溶液至终浓度100μmol.L-1。通过溴化噻唑基蓝四唑(MTT)法和Millicell小室观察VSMC的增殖和迁移变化,免疫印迹(Western blotting)检测VSMC内平滑肌α肌动蛋白、SM22α、骨桥蛋白、p38和ERK1/2丝裂素活化蛋白激酶(MAPK)信号通路表达差异。结果 MEF2A基因△21突变可促进VSMC增殖、迁移和表型转化。而阿托伐他汀可抑制这些变化,并且明显下调磷酸化p38和ERK1/2信号通路表达。结论阿托伐他汀通过作用于p38和ERK1/2MAPK信号通路,以抑制MEF2A基因突变诱导的VSMC增殖、迁移和表型转化。
Objective To investigate the effect of atorvastatin on mutant vascular smooth muscle cells (VSMC) with myofibrillar 2A (MEF2A) gene. Methods Human aortic vascular smooth muscle cells were divided into three groups: ① WT group transfected with wild type (WT) MEF2A plasmid; ②Δ21 group transfected with 21 base deletion mutant (△ 21) MEF2A plasmid; ③ Atorvastatin Statin group, MEF2A △ 21 plasmid was transfected, and atorvastatin solution was added to the group of cell culture medium to the final concentration of 100μmol.L-1 before experiment. The proliferation and migration of VSMCs were observed by MTT method and Millicell chamber. The expressions of α-actin, SM22α, osteopontin, p38 and ERK1 / 2 in VSMC were detected by Western blotting Cleavage - activated protein kinase (MAPK) signaling pathway differences in expression. Results The △ 21 mutation of MEF2A gene can promote VSMC proliferation, migration and phenotypic transformation. Atorvastatin inhibited these changes and significantly down-regulated phosphorylated p38 and ERK1 / 2 signaling pathways. Conclusions Atorvastatin can inhibit the proliferation, migration and phenotype of VSMC induced by MEF2A gene mutation by acting on the p38 and ERK1 / 2MAPK signaling pathways.