辛伐他汀对血管平滑肌细胞增殖和迁移的影响
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Effect of Simvastatin on the Proliferation and Migration of Vascular Smooth Muscle Cells
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    摘要:

    目的观察辛伐他汀对血管平滑肌细胞增殖、迁移及血管内皮生长因子表达的影响。方法体外培养大鼠原代血管平滑肌细胞,体内建立大鼠动脉粥样硬化血管损伤模型,分为正常对照组、动脉粥样硬化损伤组、低剂量和高剂量辛伐他汀组。4周后处死动物,酶法测定血脂水平,检测胸主动脉和左颈总动脉内膜/(内膜+中膜)比值,免疫组织化学和逆转录聚合酶链反应法检测血管内皮生长因子的表达。结果辛伐他汀对血管平滑肌细胞的增殖和迁移无双向调节作用。小剂量辛伐他汀对血管平滑肌细胞的增殖和迁移无促进作用,大剂量辛伐他汀抑制血管平滑肌细胞的增殖和迁移,且随着时间延长和浓度增加其抑制作用增强,这种作用不依赖辛伐他汀的调脂性。辛伐他汀能减少血管平滑肌细胞血管内皮生长因子的表达,且高浓度的辛伐他汀显著减少血管内皮生长因子的表达。结论辛伐他汀可能通过减少血管平滑肌细胞血管内皮生长因子的表达来抑制血管平滑肌细胞的增殖和迁移。

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    Aim To investigate the effect of simvastatin on the proliferation and migration of vascular smooth muscle cells and the expression of vascular endothelial growth factor mRNA. Methods The atherosclerotic vessel injured model was established and male Sprague-Dawley rats were divided into four groups randomly: normal control group, atherosclerotic injured group, low dose simvastatin group and high dose simvastatin group. The rats were put to death after 4 weeks. The serum lipid and the ratio of intima/ (intima + media) of thoracic aorta and left common carotid artery were detected, the expression of vascular endothelial growth factor on blood vessel was determined by immunohistochemistory and RT-PCR method. Results Simvastatin didn’t show biphasic effect on the proliferation and migration of vascular smooth muscle cells. Low dose simvastatin didn’t promote the proliferation and migration of vascular smooth muscle cells, while high dose simvastatin showed inhibition effect on the proliferation and migration of vascular smooth muscle cells, which was independent on lipid decreased. Simvastatin could diminish the vascular endothelial growth factor mRNA expression of vascular smooth muscle cells. Moreover, high dose simvastatin could significantly decrease the vascular endothelial growth factor mRNA expression. Conclusions Simvastatin might have inhibitive effect on vascular smooth muscle cells by decreasing the expression of vascular endothelial growth factor in vascular smooth muscle cells.

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张丽丽,戴秋艳.辛伐他汀对血管平滑肌细胞增殖和迁移的影响[J].中国动脉硬化杂志,2008,16(12):943~947.

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  • 收稿日期:2008-09-03
  • 最后修改日期:2008-11-18
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