阿伐他汀对自发性高血压大鼠心肌成纤维细胞增殖及胶原合成的影响

Effects of Atorvastatin on the Proliferation and Collagen Synthesis in Cultured Cardiac Fibroblasts from Spontaneously Hypertensive Rats

  • 摘要: 目的 探讨阿伐他汀 (atorvastatin)对培养的自发性高血压大鼠 (spontaneoushypertensiverats,SHR)和正常血压Wistar大鼠心肌成纤维细胞 (cardiacfibroblasts ,CFs)增殖和胶原合成的影响。方法 采用胰酶消化法培养CFs,用四甲基偶氮唑蓝(MTT)比色法测定细胞增殖 ,流式细胞分析仪 (FCM)技术检测细胞周期 ,ELISA法检测Ⅰ型胶原合成。结果  (1) 10 -7mol/L、10 -6mol/L、10 -5mol/L和 10 -4mol/L阿伐他汀作用后MTT比色法A比值 :SHR组分别为 0 30± 0 0 1、0 2 6± 0 0 1、0 2 4±0 0 1和 0 2 2± 0 0 1,与对照组 (0 33± 0 0 1)比较差异非常显著 (P均 <0 0 1) ;Wistar大鼠组分别为 0 2 8± 0 0 1、0 2 6± 0 0 1、0 2 3± 0 0 1和 0 2 1± 0 0 1,与对照组 (0 30± 0 0 1)相比差异非常显著 (P均 <0 0 1)。 (2 ) 10 -6mol/L阿伐他汀作用 4 8h,SHR和Wistar大鼠CFs的G0 /G1期细胞百分率均较对照组显著增高 (P均 <0 0 1) ,S期细胞百分率、G2 /M期细胞百分率和增殖指数 (proliferationindex,PI)则较对照组显著降低(P均 <0 0 1)。 (3)随着阿伐他汀浓度的增高 ,CFs的Ⅰ型胶原分泌呈明显的递减趋势。 10 -7mol/L、10 -6mol/L、10 -5mol/L和 10 -4mol/L阿伐他汀作

     

    Abstract: Objective To investigate the effects of atorvastatin on the proliferation and collagen synthesis in cultured rat cardiac fibroblasts (CFs). Methods CFs were enzymatically isolated from 12-week-old spontaneously hypertensive rats (SHR) and Wistar rats. Cell proliferation was evaluated by MTT assay and cell cycle distribution was determined with flow cytometer (FCM). Collagen synthesis was measured by ELISA. Results (1) “A” values of CFs from SHR measured with MTT assay in the 10 -7 mol/L,10 -6 mol/L,10 -5 mol/L and 10 -4 mol/L atorvastatin groups were 0.30±0.01,0.26±0.01,0.24±0.01 and 0.22±0.01,respectively,which were all significantly lower than that of control group (0.33±0.01,all P <0.01). “A” values of CFs from Wistar were 0.28±0.01,0.26±0.01,0.23±0.01 and 0.21±0.01,respectively,which were all remarkably lower than that of control group (0.30±0.01,all P <0.01). (2) 10 -6 mol/L atorvastatin could increase the percentage of G0/G1 stage and decrease the percentage of S stage,G2/M stage and proliferation index (PI). (3) The contents of collagen Ⅰ secreted by CFs from SHR and Wistar rats in 10 -7 mol/L-10 -4 mol/L atorvastatin groups were significantly lower than those of control groups (all P <0.01). Conclusion Atorvastatin dose-dependently inhibite the proliferation and collagen synthesis in cultured rat CFs. CFs from SHR were more sensitive to atorvastatin than those from Wistar rats.

     

/

返回文章
返回