辛伐他汀和西立伐他汀对体外培养血管平滑肌细胞增殖及迁移的影响

Effect of simvastatin and cerivastatin on proliferation and migration of cultured vascular smooth muscle cells

目的 :观察辛伐他汀和西立伐他汀对血管平滑肌细胞 (vascularsmoothmusclecell,VSMC)增殖和迁移的影响。以探讨他汀类药可能的非调脂抗动脉粥样硬化作用。方法 :采用体外兔髂动脉VSMC培养技术 ,以3H TdR的参入量表示VSMC的DNA合成情况 ,以Sarkar建立的方法测定VSMC的迁移距离 ,观察辛伐他汀和西立伐他汀对VSMC增殖和迁移的影响。结果 :辛伐他汀 10 -8～ 10 -5mol·L-1对VSMCDNA合成的抑制率为 14.0 %～78.8% ,西立伐他汀 10 -9～ 10 -6mol·L-1对VSMCDNA合成的抑制率为 0 .9%～ 6 3 .6 % ;辛伐他汀 10 -6～ 10 -5mol·L-1、西立伐他汀 10 -7～ 10 -6mol·L-1明显抑制VSMC迁移。两种药物对VSMC增殖和迁移的抑制呈剂量依赖关系。结论 :辛伐他汀和西立伐他汀可剂量依赖性地抑制VSMC的增殖和迁移 ,这种非调脂作用可能在延缓动脉粥样硬化发生、发展 ,减少再狭窄发生率或减轻再狭窄病变方面有积极影响。

Objective: To investigate the effects of 3 hydroxy 3 methylglutaryl coenzyme A reductase inhibitors(statins) on anti atherosclerosis beyond their lowering cholesterol. Methods: The effects of simvastatin and cerivastatin on proliferation and migration of vascular smooth muscle cells (VSMC) were observed by means of DNA synthesis analysis of cultured VSMC ( 3H TdR incoperation) and Sarkar's technique. Results: The inhibitory rates of 14.0%- 78.8% in VSMC DNA synthesis were found in simvastatin of 10 -8 -10 -5 mol·L -1 and the inhibitory rates of 10 -9 -10 -6 mol·L -1 cerivastatin were 0.9%-63.6%. Compared with normal controls [(8.25±2.19) mm], the migration of VSMC was (6.08±1.79) mm in 10 -6 mol·L -1 simvastatin and (5.73±2.24) mm in 10 -7 mol·L -1 cerivastatin. The inhibitory effects of statins on proliferation and migration of VSMC were dose dependent. Conclusion: Inhibition of statins on VSMC can be useful in decreasing intimal hyperplasia after balloon angioplasty and explain partly the early and significant cardiovascular events reduction reported in several clinical trials of statins therapy.