阿魏酸钠抑制心肌成纤维细胞增殖的作用及机制

Effects of Sodiumferulate on the Proliferation of Cardiac Fibroblasts

目的:研究阿魏酸钠(SF)对AngⅡ诱导的心肌成纤维细胞(CFs)增殖的作用及其机制。方法:培养新生鼠心肌成纤维细胞分为3组:对照组、AngⅡ(10-7mol/L)组和AngⅡ+SF组。MTT法检测细胞增殖;流式细胞仪分析细胞周期改变;免疫荧光法检测TGFβ1蛋白表达。结果:AngⅡ作用24h后MTTOD值显著高于对照组(P<0.01)。不同浓度SF(0.04mg/ml,0.08mg/ml,0.16mg/ml)组MTTOD值均显著低于AngⅡ组(P<0.01),呈剂量依赖性。AngⅡ组S期细胞百分率明显高于对照组,G0/G1期细胞百分率则明显低于对照组(P<0.01)。AngⅡ+SF组S期细胞百分率显著低于AngⅡ组,G0/G1期细胞百分率显著高于AngⅡ组(P<0.01),且呈剂量依赖性。AngⅡ组TGFβ1蛋白表达显著高于对照组(P<0.01),AngⅡ+SF组显著低于AngⅡ组(P<0.01)。结论:阿魏酸钠可抑制AngⅡ诱导的心肌成纤维细胞增殖,其效应呈现剂量依赖性,作用机制与降低TGFβ1蛋白表达有关。

Objective： To study the effects and mechanisms of sodium ferulate（SF） on the proliferation of cardiac fibroblasts（CFS） induced by Ang Ⅱ. Methods： Cultured cardiac fibroblasts were respectively treated for 24 hours with 10^-7 mmol/L angiotensin Ⅱ , 0. 04 mg/ml SF ＋ angiotensin Ⅱ , 0.08 mg/ml SF ＋angiotensin Ⅱ and 0. 16 mg/ml SF ＋angiotensin Ⅱ. CFs prolifertion was measured by thiazolyl blue（MTT） assay. Cell cyclin distribution was determined with flow cytometry. The expression of TGF-β1 was detected by immunofluorescence staining. Results： MTT-OD value of Ang Ⅱ Group was significantly higher than that of the control group （P 〈 0. 01）. SF （0.04-0. 16 mg/ml） decreased MTT-OD value stimulated by angiotensin Ⅱ through a dose dependent way （P〈0.01） . （2）In AngⅡ group, the percentage of CFs in S stage was significantly higher than in control group and the percentage of CFs in of G0/G1 stage was significantly lower than in control group （P〈0. 01）. In Ang Ⅱ ＋ SF （0. 04 mg/ml, 0. 08mg/ml, 0. 16 mg/ml） groups, the percentage of CFs in S stage was significantly lower than in Ang Ⅱ group and the percentage of CFs in G0/G1 stage was significantly higher than in control group. TGF-β1 protein express of AngⅡ group was significantly higher than that of control group （P〈0.01） ; TGF-β1 protein express of AngⅡ ＋ SF significantly lower than that of Ang Ⅱgroup （P 〈 0. 01）. Conclusion： SF inhibits effectively the prolifertion of cultured rat CFs induced by angiotensin Ⅱ through a dose dependent way,which is related to the decreasing of TGF-β1 expression.