SREBPS及VEGF调节辛伐他汀对血管平滑肌细胞的作用

目的观察辛伐他汀对血管平滑肌细胞作用,是否通过SREBPs及VEGF的调节起作用,SREBPs与VEGF之间相互关系。方法①体外培养大鼠血管平滑肌细胞(VSMCs),观察辛伐他汀对VSMCs增殖、迁移的影响及SREBPs、VEGF的mRNA表达。②建立大鼠动脉粥样硬化血管损伤模型,分为NC组、AI,组、LS组和HS组。药物干预4周后测定各组血脂、胸主动脉内膜/(内膜+中膜)比值及血管SREBPs、VEGF的mRNA表达。结果实验证明,大剂量辛伐他汀明显抑制VSMCs增殖和迁移,VSMCs的SREBP-1、SREBP-2的mRNA表达显著增加同时VEGF的表达显着减少,SREBPs与VEGF之间有一定的相关性。结论辛伐他汀抑制血管平滑肌细胞增殖和迁移机制可能是通过增加VSMCs的SREBPs的表达进而减少VEGF表达。

Effect of Sterol Regulatory Element Binding Proteins and Vascular Endothelial Growth Factor Regulating Simvastatin on Vascular Smooth Muscle Cells

Objective To investigate the biphasic effect of simvastatins on vascular smooth muscle cells （VSMCs） and the possible mechanism regulated by Sterol Regulatory Element Binding Proteins （SREBPs） and Vascular Endothelial Growth Factor （VEGF）. To explore the relationship between SREBPs and VEGF. Methods 0）To investigate the effect of simvastatin on the proliferation and migration of VSMCs and the SREBP-1, SREBP-2 and VEGF mRNA expression of VSMCs by primary VSMCs culture in vitro. 2 The atherosclerotie vessel injured model was established and randomly divide into four groups. Normal control group, atheroselerotic injured group, low-dose simvastatin group, and high-dose simvastatin group. After 4 weeks simvastatin intervention, the serum lipid and the ratio of intima/（intima ＋ tuniea media） of thoracic aorta were detected. The mRNA expression of SREBP-1, SREBP-2 and VEGF on blood vessel were also determined. Results High dose simvastatin inhibited the proliferation and migration of VSMCs. Moreover, high-concentration simvastatin could significantly activate SREBP-1 and SREBP-2 mRNA expression while obviously reduce the VEGF mRNA expression ofVSMCs. SREBPs and VEGF have some relationship. Conclusion Simvastatin inhibit the proliferation and migration of VSMCs via activating SREBPs expression and then decreasing the expression of VEGF in VSMCs.