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
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Role of simvastatin on the proliferation and migration of rat adventitial fibroblasts
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    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定作用。

    Abstract:

    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.

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金培印,马业新,高波,周强.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[J].中国动脉硬化杂志,2004,12(1):35~38.

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  • 收稿日期:2003-08-09
  • 最后修改日期:2003-12-20
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