辛伐他汀对大鼠血管外膜成纤维细胞增殖迁移和胶原合成的影响

Role of simvastatin on the proliferation and migration of rat adventitial fibroblasts

为观察辛伐他汀对血管外膜成纤维细胞增殖、迁移和胶原合成的影响 ,用组织贴块法培养SD大鼠的血管外膜成纤维细胞 ,以四氮唑蓝比色法测定细胞增殖 ,以Sarkar方法测定血管外膜成纤维细胞迁移距离 ,以3 H 脯氨酸掺入法测定胶原合成。结果发现 ,随着辛伐他汀浓度增高血管外膜成纤维细胞的A4 90值呈递减趋势 ,10 -7、10 -6、10 -5和 10 -4mol/L组的A4 90值分别为 0 .2 91± 0 .0 11、0 .2 6 5± 0 .0 0 6、0 .2 34± 0 .0 0 8和 0 .2 14± 0 .0 0 6 ,与对照组(0 .335± 0 .0 18)差异显著 (P均 <0 .0 1) ;随着辛伐他汀浓度增高血管外膜成纤维细胞的迁移距离呈递减趋势 ,10 -7、10 -6、10 -5和 10 -4mol/L组的迁移距离分别为 6 .5± 1.1mm、5 .3± 1.2mm、4 .1± 1.0mm和 2 .9± 0 .9mm ,与对照组 (8.1± 1.8mm)差异显著 (P均 <0 .0 1)。随着辛伐他汀浓度的增高的3 H 脯氨酸掺入率呈递减趋势。 10 -7、10 -6 、10 -5及 10 -4mol/L组血管外膜成纤维细胞的3 H 脯氨酸掺入率分别为 (cpm/ 5 0 0 0细胞 ) 385± 5 1、2 72± 4 8、16 1± 38和 14 1± 36 ,与对照组 (6 5 5± 5 8)差异显著 (P均 <0 .0 1)。此结果提示 ,辛伐他汀可以剂量依赖地抑制血管外膜成纤维细胞增殖、迁移和胶原合成 ,这可能对改善血管重塑有一?

Aim To investigate the effects of simvastation on the proliferation and migration of rat adventitial fibroblasts as well as collagen synthesis. Metheods Isolated vascular adventitial fibroblast (VAF) of Sprague-Dawley(SD) rats were cultured. VAF proliferation was measured by thiazolyl (MTT) blue assay. The migration of VAF was determined by Sarkar's technique. Collagen synthesis was measured by 3H-proline uptake test. Results (1)MTT colorimetry showed the A490 values were 0.291±0.011, 0.265±0.006, 0.234±0.008 and 0.214±0.006 respectively in the 10 -7 mol/L, 10 -6 mol/L, 10 -5 mol/L and 10 -4 mol/L simvatastin groups, all significantly lower than that in the control group (0.335±0.082, all P<0.01). (2)The distance of migration was 6.5±1.1 mm, 5.3±1.2 mm, 4.1±1.0 mm and 2.9±0.9 mm respectively in the 10 -7 mol/L, 10 -6 mol/L, 10 -5 mol/L and 10 -4 mol/L simvastatin groups, all significantly lower than that in the control group (8.1±1.8, all P<0.01). (3)The 3H proline uptake was (c/min)385±51, 272±48, 161±38 and 141±36 respectively in the 10 -7 mol/L, 10 -6 mol/L, 10 -5 mol/L and 10 -4 mol/L simvastatin groups, all significantly lower than that in the control group (655±58, all P<0.01). Conclusions Simvastatin can effectively inhibit the proliferation,migration and collagen synthesis of rat vascular adventitial fibroblasts in a dose-dependent manner which may play a role in ameliorating vascular remodeling.