摘要
目的:探讨阿托伐他汀对心脏成纤维细胞转化生长因子-β1(TGF-β1)合成和分泌的影响。方法:将心脏成纤维细胞分6组培养:空白对照组,醛固酮组(培养液中加入醛固酮,终浓度为1×10-7mol/L),阿托伐他汀预处理Ⅰ、Ⅱ及Ⅲ组(培养液中加入阿托伐他汀,终浓度分别为1×10-6、1×10-5及1×10-4mol/L,24h后加入醛固酮)及阿托伐他汀+甲羟戊酸组(培养液中加入阿托伐他汀,终浓度为1×10-4mol/L,甲羟戊酸,终浓度为1×10-3mol/L,24h后加入醛固酮)。ELISA法测定培养液中TGF-β1蛋白水平,RT-PCR和WesternBlot法分别测定心脏成纤维细胞中TGF-β1mRNA和蛋白的表达。结果:6组心脏成纤维细胞TGF-β1mRNA表达、蛋白合成和分泌水平差异均有统计学意义(F值分别为104.534,30.405和14.418,P均<0.001)。与空白对照组比较,醛固酮组和阿托伐他汀+甲羟戊酸组TGF-β1mRNA表达量、TGF-β1蛋白表达和分泌水平增加(P均<0.01);阿托伐他汀预处理组上述3个指标低于醛固酮组和阿托伐他汀+甲羟戊酸组(P均<0.01)。结论:阿托伐他汀可能通过甲羟戊酸代谢途径,抑制醛固酮诱导的心脏成纤维细胞TGF-β1mRNA的表达以及TGF-β1蛋白的合成和分泌。
Aim：To investigate the effects of atorvastatin on the transforming growth factor-beta 1（TGF-β1） expression in cardiac fibroblasts.Methods：Cardiac fibroblasts were allocated into 6 groups.The control group was cultured with normal medium.Aldosterone group was induced by 10-7 mol/L aldosterone.Atorvastatin pretreatment Ⅰ,Ⅱ and Ⅲ groups were pretreated with atorvastatin at dose of 1×10-6,1×10-5,and 1×10-4 mol/L,respectively,then induced by aldosterone.Atorvastatin＋mevalonate group was pretreated with 1×10-4 mol/L atorvastatin and 1×10-3 mol/L mevalonate,then induced by aldosterone.TGF-β1 concentration in conditioned medium was measured by ELISA,intracellular TGF-β1 level was evaluated by Western Blot,and the expression of TGF-β1 mRNA was detected using RT-PCR.Results：There were significant differences in the intracellular TGF-β1 level of protein and mRNA,and TGF-β1 concentration in conditioned medium（F was 104.534,30.405 and 14.418,respectively,P0.001）.Aldosterone could significantly up-regulate TGF-β1 mRNA expression and the protein synthesis and secretion of cardiac fibroblasts（P0.01）.Atorvastatin could block these effects（P0.01）.In contrast,atorvastatin-induced inhibitory effects were reversed in the presence of mevalonate（P0.01）.Conclusion：Atorvastatin could down-regulate TGF-β1 mRNA expression,as well as TGF-β1 synthesis and secretion induced by aldosterone in a process specifically related to mevalonate in cardiac fibroblasts.
出处
《郑州大学学报（医学版）》
CAS
北大核心
2010年第1期51-53,共3页
Journal of Zhengzhou University(Medical Sciences)
基金
河北省教育厅基金资助项目ZH2006004
