目的:观察辛伐他汀对血管平滑肌细胞(VSMC)增殖中FGFRI、p21ras蛋白表达的影响.方法:体外培养大鼠VSMC,建立VSMC增殖模型,应用不同浓度的辛伐他汀干预,MTT法测定细胞增殖活力;免疫印迹法检测FGFR1与p21ras蛋白的表达.结果:与对照组比较.辛伐他汀各浓度组细胞增殖活力均显著降低(P<0.05);与对照组(FGFR1 208.07±10.70,p21ras 202.43±12.36)相比,低剂量组(FGFR1 181.47±7.43,p21ras 182.00±8.98)的FGFR1、p21ras表达差异无显著性(P>0.05),中剂量组(FGFR1 144.90±9.03,p21ras147.03±9.13)、高剂量组(FGFR1 104.43±8.08,p21ras 100.3 ±8.37)的表达均较明显降低(P<0.05),中、高剂量组FGFR1、p21ras表达较低剂量组均显著降低(P<0.05),高剂量组表达又较中剂量组显著降低(P<0.05),呈剂量依赖性.结论:辛伐他汀能抑制VSMC增殖,该作用是通过抑制FGFR1、p21ras蛋白表达实现的,这可能是辛伐他汀治疗动脉粥样硬化、再狭窄及高血压等心血管疾病的重要机制之一.%Objective To investigate the effect of simvastatin on the proliferations and the expressions of FGFR1 and p21ras in rats vascular smooth muscle cells (VSMCs). Methods VSMCs were cultivated in vitro and VSMC models of proliferation were established in the study. The alive cells counting by tetrazolium dye-reduction assay (MTT) were use to determine the effect of simvastatin on VSMCs proliferation at different concentrations (0, 1, 5, 10 μmol/L), the expressions of FGFR1 and p21ras were detected by Western blot methods. Results Compared with the control group, other simvastatin concentration groups were appeared different levels of growth inhibition (P < 0.05); Compared with the control group, the expressions of FGFR1, p21ras was unconspicuously changed in low dose group while the expressions were more significantly reduced in middle dose and high dose groups (P < 0.05); Compared with middle dose group, the expression was clearly reduced in high dose group group (P < 0.05), and there was a obvious dose dependency. Conclusions Simvastatin might play a role of inhibiting VSMCs proliferation by reducing the expression of FGFR1 and p21ras, it may be one of the important mechanisms that simvastatin treated cardiovascular disease such as atherosclerosis, restenosis and hypertension.
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