阿托伐他汀对血管平滑肌细胞增殖和血红素氧化酶1表达的影响

Effect of Aorvastatin on the VSMC Proliferation and HO-1 Expression

目的探讨阿托伐他汀对血管平滑肌细胞增殖的影响及对血红素氧化酶1（HO-1）表达的作用。方法采用酶消化法分离大鼠血管平滑肌细胞。取4－6代细胞用于实验,胰岛素样生长因子1（IGF-1）刺激血管平滑肌细胞增殖,以不同浓度（0、0.01、0.1、1和10μmol/L）阿托伐他汀、10μmol/L阿托伐他汀＋锌原卟啉Ⅸ（ZNPPⅨ）进行干预。采用四唑盐（MTT）比色法观察细胞的增殖。逆转录聚合酶链反应（RT-PCR）半定量分析细胞HO-1 mRNA的表达。结果IGF-1可促进血管平滑肌细胞增殖,与空白组比较,IGF-1组细胞计数明显增加（P〈0.01）,随着阿托伐他汀浓度的提高,血管平滑肌细胞计数逐渐减少（P〈0.01）,加入ZNPPⅨ后血管平滑肌细胞增殖恢复。空白组和IGF-1组血管平滑肌细胞HO-1有少量表达,随着阿托伐他汀浓度的增加,HO-1的表达增强,呈剂量依赖性。与空白组和IGF-1组比较,0.01μmol/L组HO-1增加不明显,0.1μmol/L组HO-1开始有较明显增加,10μmol/L组HO-1表达达高峰（P〈0.01）。结论阿托伐他汀可抑制血管平滑肌细胞的增殖和诱导HO-1的表达。诱导HO-1表达是阿托伐他汀抑制血管平滑肌细胞增殖的机制之一。

Objective To study the effect of atorvastatin on the proliferation of vascular smooth muscle cells （ VSMC ） and the expression of heine oxygenase - 1 （ HO - 1 ）. Methods VSMC cultured from SD rats were cultured by enzymatic dissociation methods. The purity of cultured VSMC was assessed morphyologically and confirmed by immunecytochemical staining for α - actin. Subcultures between 4 and 6 were used in the study. Insulin - like growth factor - 1 （ IGF - 1 ） was used to stimulate VSMC proliferation. The alive cell counting by tetrazolium dye - reduction assay（MTT） were used to determine the effect of arorvastatin on VSMC proliferation at different concentration （0, 0. 01,0. 1,1,10 μmol/L ）, the same methods were used to do with 10 μmol/L atorvastatin in combination with ZnPPIX. The level of HO - lmRNA were assessed by the method of RT - PCR. Results Proliferation of VSMC were decreased with the increase of atorvastatin concentration. ZnPPIX, a special inhibitor of HO - 1 ,could partially reverse the inhibition of atorvastatin. The increase of the expression in HO - 1 （ IGF - 1 ） was dependent on the dose of atorvastatin. Conclusion Atrovastatin could inhibit VSMC proliferation and induce the expression of HO - 1. Inducing HO - 1 expression was one of the mechanisms responsi- ble for atorvastatin inhibiting VSMC proliferation.