HMG-CoA还原酶抑制剂对自发性高血压大鼠血管平滑肌细胞增殖的作用

Effects of HMG-CoA Reductase Inhibitors on Proliferation of Vascular Smooth Muscle Cells from Spontaneously Hypertensive Rats

探讨羟甲基戊二酰辅酶A还原酶抑制剂对自发性高血压大鼠血管平滑肌细胞增殖的抑制作用及其机制。培养自发性高血压大鼠主动脉血管平滑肌细胞 ,应用不同浓度HMG CoA还原酶抑制剂洛伐他汀、辛伐他汀和氟伐他汀及血管紧张素Ⅱ、甲羟戊酸等干预后 ,进行细胞计数和 3 H TdR掺入率测定。结果发现 ,洛伐他汀、辛伐他汀和氟伐他汀均呈浓度依赖性抑制小牛血清和血管紧张素Ⅱ诱导的血管平滑肌细胞数和 3 H TdR掺入率增加 ;但以氟伐他汀的抑制作用最大 ,辛伐他汀次之 ,洛伐他汀最小。 10 - 3 mol L甲羟戊酸几乎完全逆转洛伐他汀、辛伐他汀和氟伐他汀对血管平滑肌细胞增殖的抑制作用。提示此 3种HMG CoA还原酶抑制剂均能抑制高血压大鼠血管平滑肌细胞增殖 ,但作用并不完全相同 ;甲羟戊酸代谢途径可能参与血管平滑肌细胞增殖过程。

Aim To investigate the effects of fluvastatin, simvastatin and lovastatin on the proliferation of vascular smooth muscle cells derived from spontaneously hypertensive rats. Methods The aorta smooth muscle cells(ASMC) from spontaneously hypertensive rats were cultured, and proliferation of cells were detected by cell number counting and 3 H-thymidine( 3H-TdR) incorporation after incubation with AngⅡ, fluvastatin, simvastatin, lovastatin and mevalonate acid. Results The increased cell number and 3 H-TdR incorporation stimulated with 2%FCS and AngⅡ(10 -6 mol/L) were significantly inhibited by three agents in a concentration-dependent manner (10 -5 ～10 -7 mol/L), but the inhibitory efficacy was fluvastatin>simvastatin>lovastatin. The inhibitory effects were completely reversed by mevalonate acid(10 -3 mol/L). Conclusions The proliferation of SHR ASMC was inhibited by fluvastatin, simvastatin and lovastatin, which suggested that mevalonate acid pathway may play an important role in the proliferation of SHR ASMC.