辛伐他汀对结缔组织生长因子诱导大鼠心肌细胞肥大的影响及其与ERK1/2的关系  

Effects of simvastatin on hypertrophic cardiac myocytes induced by connective tissue growth factor and its relation with ERK1/2

作　　者：刘慧[1] 卢少平[1] 尚福军[1] 牛晓琳[1] 艾永飞[1] 赵连友[1] 

机构地区：[1]第四军医大学唐都医院心内科,西安710038

出　　处：《山西医科大学学报》2016年第6期489-492,共4页Journal of Shanxi Medical University

摘　　要：目的观察辛伐他汀对结缔组织生长因子(CTGF)诱导大鼠心肌细胞肥大的影响,探讨其作用与细胞外信号调节激酶1/2(ERK1/2)的关系。方法以培养的新生的SD大鼠心肌细胞为实验模型,分为对照组(DMEM培养液)、CTGF(50ng/L)刺激组、CTGF+不同浓度辛伐他汀(Sim)组,分别用图像分析法测定心肌细胞表面积,[~3H]-亮氨酸掺入法测定心肌细胞蛋白合成速率,考马斯亮兰法测定心肌细胞蛋白含量,蛋白免疫印迹法测定心肌细胞总ERK1/2(t-ERK1/2)和磷酸化ERK1/2(pERK1/2)蛋白表达水平。结果 CTGF组的心肌细胞表面积、[3H]-亮氨酸掺入率、心肌细胞蛋白含量和p-ERK1/2表达均显著高于对照组(P<0.01);CTGF+不同浓度辛伐他汀(Sim)组的心肌细胞表面积、[3H]-亮氨酸掺入率、心肌细胞蛋白含量和pERK1/2表达分别与CTGF组比较均明显降低(P<0.01),而且随着Sim剂量逐渐增加时,这些指标也随之逐渐下降,除CTGF+10^(-5)mol/L Sim组和CTGF+10^(-4)mol/L Sim组之间的细胞蛋白含量无明显差异外,各Sim组间差异具有统计学意义(P<0.05或P<0.01);且以上各项指标在CTGF+10^(-4)mol/L Sim组与对照组均无显著差异。t-ERK1/2的表达在各实验组间均无差异。结论辛伐他汀可剂量依赖性地抑制CTGF诱导的心肌细胞肥大,其作用机制可能与ERK1/2磷酸化有关。Objective To explore the effects of simvastatin on cardiac myocytes hypertrophy induced by connective tissue growth factor（CTGF）and its relationship with ERK1 / 2. Methods The neonatal Sprague-Daley（SD）rats cardiomyocytes were divided into six groups：control group（cultured with DMEM）,CTGF（50 ng / L）group and CTGF ＋ different concentrations of simvastin groups. Image analysis system was used to measure the cell surface area. [~3H]-leucine incorporation method was used to measure protein synthesis rate of myocytes. Coomassie brilliant blue method was used to measure contents of cardiac myocytes protein. Western blot was used to study the protein expression levels of t-ERK1 / 2 and p-ERK1 / 2. Results Compared with control group,the myocardial cell surface area,[~3H]-leucine incorporation rate,myocardial cell protein contents and p-ERK1 / 2 expression were significantly increased in CTGF group（P 0. 01）. The myocardial cell surface area,[3H]-leucine incorporation rate,myocardial cell protein and P-ERK1 / 2 expression in CTGF ＋ different concentrations of Sim groups were significantly lower than in CTGF group（P 0. 01）,and these indexes were also gradually decreased with the increase of dose of Sim. The content of cardiac myocytes proteins was significantly different between different concentrations groups（P 0. 05,P 0. 01）except beween CTGF ＋ 10^（-5）mol / L Sim group and CTGF ＋ 10^（-4）mol / L Sim group. The above indexes showed no difference between CTGF ＋ 10^（-4）mol / L Sim group and control group. The expression of t-ERK1 /2 showed no difference among six groups. Conclusion Simvastatin could inhibit CTGF-induced myocyte hypertrophy in a dose dependent manner,which may be related to ERK1 / 2 phosphorylation.

关 键 词：结缔组织生长因子 辛伐他汀 心肌细胞肥大 信号转导 ERK1/2 

分 类 号：R363[医药卫生—病理学]