辛伐他汀对鼠血管成纤维细胞胶原合成的影响及甲羟戊酸的干预作用

Effects of Simvastatin on the Collagen Synthesis of Vascular Fibroblasts and Interference of Mevalonate

目的 探讨辛伐他汀（Sim）对鼠血管成纤维细胞（VFs）胶原合成的影响及甲羟戊酸（MVA）的干预效应，为防治动脉粥样硬化（AS）提供理论依据。方法采用胰酶消化、组织块贴壁法培养Wistar大鼠VFs，以^3H-脯氨酸掺入法测定胶原合成，观察不同浓度Sim分别作用不同时间对VFs胶原合成作用的影响以及MVA干预作用。结果（1）在10^-7～10^-4mol／LSim作用下，VFs^3 H-脯氨酸掺入率随着Sim干预浓度的增加而降低；（2）随着Sim（10^-5 mol／L）作用时间的延长，VFs的。H-脯氨酸掺入率呈递减趋势，VFs胶原合成功能与时间呈明显的负相关（r=-0．952，P〈0．01）。（3）MVA10^-6～10^-3 mol／L与10^-5 mol／L Sim共作用，VFs的^3H-脯氨酸掺入率随着MVA干预浓度的增高逐渐增加；（4）随着MVA作用时间的延长（6～48h），VFs的^3H-脯氨酸掺入率亦逐渐增加，VFs胶原合成功能与MVA作用时间呈显著的正相关（r=0．931，P〈0．01）。结论Sim呈浓度时间依赖性抑制VFs^3H-脯氨酸掺入率的作用可被MVA所拮抗，提示Sim减弱VFs胶原合成与MVA代谢途径密切相关。

Objective To investigate the effects of simvastatin on the collagen synthesis of vascular fibroblasts （VFs） and the interference effects of Mevalonate. Methods VFs of Wistar rats were isolated by trypsin digestion and were eoeultured with different concentrations and time of Sire and/or MVA. Collagen synthesis was measured by ^3 H-proline incorporation. Results （ 1 ） Sire decreased ^3 H-thymidine incorporation in VFs in a concentration dependent manner. （2） VFs ^3 H-thymidine incorporation of VFs decrease gradually with the increase of time. Negative correlation between ^3 H-thymidine incorporation and time was found（r=-0.952, P〈0.01）. （3） ^3H-proline incorporation of VFs increases with MVA concentration rises （P〈0.05）. （4） The effects of MVA 10^-3 mol/L on ^3H-Proline incorporation of VFs increases with the increases of cultured time （r=0. 931, P〈0.01）. Conclusion Sire decreases VFs collagen synthesis which was inhibited by the interference of MVA.