瑞舒伐他汀抑制血小板衍生生长因子诱导的血管平滑肌细胞的增殖和迁移

摘要

目的：探讨瑞舒伐他汀对血管平滑肌细胞增殖和迁移的影响及其分子机制。方法：采用血小板衍生生长因子（PDGF）-BB预处理血管平滑肌细胞，观察其对血管平滑肌细胞的增殖和迁移的作用，以及对基质金属蛋白酶（MMP）2、MMP9的表达、ERK1/2和P38蛋白的磷酸化水平的影响。结果：血小板衍生生长因子（PDGF）-BB处理后，血管平滑肌细胞的增殖和迁移明显上调，并伴随着细胞去分化为增殖型表型。而瑞舒伐他汀能显著抑制PDGF-BB诱导的血管平滑肌细胞的增殖、迁移以及表型转变；瑞舒伐他汀可抑制PDGF-BB诱导的血管平滑肌细胞中基质金属蛋白酶（MMP ）2、MMP9的表达，并下调E RK1/2和P38蛋白的磷酸化水平。结论：瑞舒伐他汀可能通过部分下调PDGF-BB诱导的MAPK信号通路活性及MMP2、MMP9的表达，从而抑制血管平滑肌细胞的异常增殖和迁移，提示瑞舒伐他汀对内膜增生相关的动脉粥样硬化和介入后再狭窄具有治疗作用。%Aim:To evalute the effect of rosuvastatin on the vascular smooth muscle proliferation and migration as well as the involved molecular mechanisms.Methods:Vascular smooth muscle was pretrea-ted with platelet-derived growth factor (PDGF)-BB.Then proliferation and migration of vascular smooth muscle cell,the protein expression of matrix metalloproteinase (MMP)2 and MMP9,as well as the phosphorylation levels of ERK1 /2 and P38 in vascular smooth muscle cells were observed.Results:This study showed that under the treatment of PDGF-BB,the proliferation and migration of vascular smooth muscle cell significantly increased,along with these cells differentiating into the proliferative phenotype. However,rosuvastatin significantly inhibited PDGF-BB-induced vascular smooth muscle cell prolifera-tion,migration,and the phenotypic change mentioned above.Further studies showed that rosuvastatin in-hibited PDGF-BB-induced the protein expression of matrix metalloproteinase (MMP)2 and MMP9,as well as the phosphorylation levels of ERK1 /2 and P38 in vascular smooth muscle cells.Conclusion:It suggested that rosuvastatin inhibited PDGF-BB-induced vascular smooth muscle cell proliferation and mi-gration,probably through downregulating the activity of MAPK signaling pathway and the protein expres-sion of MMP2 and MMP9 ,indicating that rosuvastatin may have therapeutic effects on atherosclerosis and restenosis after intervention,which are associated with intimal hyperplasia.