南方医科大学学报

南方医科大学学报 ›› 2006, Vol. 26 ›› Issue (02): 205-.

• • 上一篇    下一篇

辛伐他汀对鼠心脏成纤维细胞DNA合成的影响

徐琳； 李志梁； 赵连友； 刘映峰； 李公信； 丁明学； 赵一俏； 傅强； 赵霞；   

  1. 南方医科大学珠江医院心脏内科； 第四军医大学唐都医院心脏内科； 南方医科大学珠江医院心脏内科 广东广州510282； 广东广州510282； 陕西西安710038；
  • 出版日期:2006-02-20 发布日期:2006-02-20
  • 基金资助:
    广东省科技计划项目(2005B30601016)~~

Effects of simvastatin on DNA synthesis in rat cardiac fibroblasts

XU Lin, LI Zhi-liang, ZHAO Lian-you, LIU Ying-feng, LI Gong-xin, DING Ming-xue, ZHAO Yi-qiao, FU Qiang, ZHAO Xia Department of Cardiology, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China; Department of Cardiology, Tangdu Hospital, Fourth Military Medical University, Xi’an 710038, China   

  1. 南方医科大学珠江医院心脏内科； 第四军医大学唐都医院心脏内科； 南方医科大学珠江医院心脏内科 广东广州510282； 广东广州510282； 陕西西安710038；
  • Online:2006-02-20 Published:2006-02-20

PDF

1063

摘要： 目的探讨辛伐他汀(Sim)对新生SD大鼠心脏成纤维细胞(CFs)DNA合成的影响及甲羟戊酸(MVA)的干预效应。方法采用胰酶消化、差速贴壁法培养新生SD大鼠CFs,以3H-胸腺嘧啶核苷(3H-TdR)掺入法测定DNA合成,观察不同浓度Sim及MVA分别作用不同时间对CFsDNA合成功能的影响。结果 (1)CFs的3H-TdR掺入率随着Sim干预浓度的增加而降低,其中10-6和10-5mol／L Sim组的3H-TdR掺入率分别为(1175±202．66)、(771±164．86)cpm／2000细胞, 显著低于对照组的(1608±204．32)cpm／2000细胞(均P<0．01);(2)10-5mol／L Sim作用CFs 6、12、18、24、30、36、42、48 h, 随着Sim作用时间的延长,CFs的3H-TdR掺入率呈递减趋势,与时间呈明显的负相关(r=-919,P<0．01);(3)CFs的3H-TdR 掺入率随着MVA干预浓度的增加呈进行性上升,其中10-4、10-3 mol／L MVA+10-5 mol／LSim组3H-TdR掺入率分别为 (1612±308．57)、(1995±353．83)cpm／2000细胞,显著高于对照10-5mol/L Sim组的(771±164．86)cpm／2000细胞(P<0．01); (4)10-3 mol／L MVA分别作用CFs 6-48 h,CFs的3H-TdR掺入率随着MVA作用时间的延长而逐渐增加,呈明显的正相关(r=0．968,P<0．01)。结论 Sim呈浓度-时间依赖方式抑制CFs DNA的合成且可被MVA拮抗,提示Sim可抑制CFs 增殖,延缓心肌纤维化,其作用可能通过MVA途径实现。 

Abstract: Objective To investigate the effects of simvastatin (Sim) and the interference by mevalonate (MVA) against its effect on DNA synthesis in rat cardiac fibroblasts (CFs). Methods CFs were isolated from neonatal SD rats by trypsin digestion and growth-arrested CFs were stimulated with Sim and/or MVA at varied concentrations for different time lengths, and the DNA synthesis in the cells was measured by 3H-thymidine (3H-TdR) incorporation assay. Results Sim decreased 3H-TdR incorporation in the CFs in a concentration-dependent manner, and 3H-TdR incorporation was significantly lower in cells treated with 1×10-6 and 1×10-5 mol/L Sim (1 175±202.66 and 771±164.86 cpm/2000 cells, respectively) than in the control cells (1 608±204.32 cpm/2000 cells, P<0.01). As the treatment time with 1×10-5 mol/L Sim prolonged (for 6, 12, 18, 24, 36, 42, and 48 h), 3H-TdR incorporation in CFs decreased gradually, showing an obvious inverse correlation with the treatment time (r=-919, P<0.01). 3H-TdR incorporation in cells treated with 1×10-6 to 1×10-3 mol/L MVA and 1×10-5 mol/L Sim rose steadily as MVA concentration increased. A significant difference in the incorporation was found between cells treated with both 1×10-4/1×10-3 mol/L MVA and 1×10-5 mol/L Sim (1 612±308.57 and 1 995±353.83 cpm/2000 cells, respectively) and the cells with 1×10-5 mol/L Sim treatment alone (P<0.01); difference was also noted between cells treated with 1×10-5 mol/L MVA and the control cells (P<0.05), but treatment with 1×10-6 mol/L MVA did not produce much difference in comparison with the control cells (P>0.05) With the increase of treatment time (for 6, 12, 18, 24, 36, 42, 48h), 1×10-3 mol/L MVA caused steady increase in 3H-TdR incorporation in the CFs, showing a significant positive correlation with the treatment time (r=0.968, P<0.01). Conclusion Sim can decrease DNA synthesis in rat CFs and postpone the occurrence of myocardial fibrosis, which can be reversed by MVA. 更多

中图分类号: