摘要
目的观察细胞因子心肌营养素1(CT-1)诱导大鼠心肌细胞的肥大效应,探讨辛伐他汀(Sim)对这一过程的干预作用及其信号转导机制。方法以培养的新生Sprague-Dawley(SD)大鼠心肌细胞为实验模型,分为对照组,CT-1诱导组,CT-1+Sim组,CT-1+Sim+甲羟戊酸(MVA)组,CT-1+AG490(JAK2拮抗剂)组。应用图像分析系统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,逆转录聚合酶链式反应(RT-PCR)检测心钠素(ANP)mRNA表达,RT-PCR检测细胞因子信号通路JAK/STAT的mRNA表达水平。结果(1)与对照组相比,CT-1组心肌细胞表面积,3H-亮氨酸掺入率,ANPmRNA表达水平均明显增高(P<0.01),JAK2拮抗剂AG490可显著的抑制CT-1的作用(P<0.01)。(2)与CT-1组相比,辛伐他汀共培养后心肌细胞表面积,3H-亮氨酸掺入率,ANPmRNA表达水平明显减小(P<0.01),外源性甲羟戊酸可显著的抑制辛伐他汀的作用(P<0.01);(3)CT-1可使心肌细胞JAK-STAT的mRNA表达水平显著增强,辛伐他汀显著抑制CT-1诱导心肌细胞JAK-STATmR-NA表达水平增高(P<0.01),而MVA和AG490可部分阻断辛伐他汀的效应(P<0.01)。结论心肌营养素1能够诱导心肌细胞肥大,辛伐他汀可抑制其这一过程并可能与细胞因子信号通路JAK-STAT活化有关。
Objective To explore the effects of simvastatin on the hypertrophy of cultured rat cardiomyocytes induced by cardiotrophin-1 （CT-1） and to investigate whether this effect was mediated via JAK STAT signaling pathway. Methods Neonatal Sprague-Dawley（SD） rat cardiac myocytes cultured with CT-1 （10 ng/mL） were treated with simvastatin; two groups of them pretreated with mevalonate plus simvastatin or AG490, a inhibitor of J AK2. Image analysis system, ^3H-leucine incorporation, RT-PCR were used to evaluate the cell surface area, protein synthesis, expression of mRNA of atrial natriuretic peptide （ANP）and JAK-STAT in cardiomyocytes. Results Simvastatin was proved to significantly decrease cardiomyocytes size as well as protein synthesis. Furthermore, simvastatin inhibit ANP mRNA synthesis and JAK-STAT mRNA expression induced by CT-1 in cardiomyocytes （P〈0. 01 ）. Mevalonate and AG490 significantly blocked the effect of simvasatin on cardiomyocytes size and protein synthesis. ANP and JAK-STAT mRNA synthesis induced by CT-1 in cardiomyocytes was attenuated by mevalonate and AG490（ P〈0. 01 ）. Conclusion These data suggest that simvastatin ameliorate cardiomyocytes hypertrophy in vitro via JAK-STAT signaling pathways. The present study may provides a novel understanding and alternative therapeutic strategy for cardiac hypertrophy.
出处
《中华高血压杂志》
CAS
CSCD
北大核心
2006年第9期743-746,共4页
Chinese Journal of Hypertension
基金
陕西省自然科学研究项目资助课题[2004C2-21]
