中国药理学通报2013，Vol.29Issue(7)：913-917,5.DOI:10.3969/j.issn.1001-1978.2013.07.007
碘化N-正丁基氟哌啶醇对血管紧张素Ⅱ诱导心肌细胞肥大的抑制作用
Inhibitory effects of N-n-butyl haloperidol iodide on cardiomyocyte hypertrophy induced by angiotensin Ⅱ
摘要
Abstract
Aim To investigate the effects of N-n-butyl haloperidol iodide ( F2 ) on angiotensin Ⅱ ( AngⅡ )-induced cardiomyocyte hypertrophy and the mechanism. Methods In the cultured rat cardiomyocyte cell line ( H9C2 ), as indexes of cardiomyocyte hypertrophy, the cell surface area of H9C2 cells was measured and the total proteins of H9C2 cells were determined by BCA method. The expression of the nuclear transcription factor, extracellular signal regulated ki-nase ( ERK ) and cAMP-response element binding pro-tein( CREB )were assessed by Western blot. Results The cell surface areas and the total proteins stimulated by Angll ( 10 -7 mol · L-1 ) with 48h in the cardiomyo-cytes of the H9C2 cells increased significantly in contrast to those of control. F2( 10 -8 , 10 -7 , 10-6 mol · L-1 ) effectively decreased the increased cell surface areas and total proteins induced by Angll in a dose-dependent manner. Angll had the effect of promoting the activation of ERK1/2 and CREB, and increased the expression of p-ERK1/2 and p-CREB. Cardiomyocytes of H9C2 cells pretreated with AngⅡ ( 10-7mol · L-1 ) for 1 min, the p-ERK1/2 and p-CREB proteins expression began to increase, the peak effect was nearly at 5 to 10 min, and the activation was lasting for about 60min. While pretreatment with F2( 10 -8 , 10 -7 , 10-6 mol · L ) for 30 min, AngⅡ-induced increase in the expression of p-ERK1/2, and p-CREB proteins were inhibited evidently by F2 in a dose-dependent manner. Conclusion The results suggest that F2 has the anti-hypertrophic effect on cardiomyocyte hypertrophy induced by AngⅡ, and the mechanism might be associated with its inhibitory effect on ERK and CREB.关键词
碘化N-正丁基氟哌啶醇/心肌细胞/细胞肥大/血管紧张素Ⅱ/细胞外信号调节激酶(ERK)/cAMP反应元件结合蛋白(CREB)Key words
N-n-butyl haloperidol iodide/ cardiomyocyte / hypertrophy/ angiotensin Ⅱ/ extracellular signal regulated kinase ( ERK )/ cAMP-response element binding protein( CREB )分类
医药卫生引用本文复制引用
黄展勤,李金玉,姜红岩,刘幸平,郑燕珊,石刚刚..碘化N-正丁基氟哌啶醇对血管紧张素Ⅱ诱导心肌细胞肥大的抑制作用[J].中国药理学通报,2013,29(7):913-917,5.基金项目
国家自然科学基金资助项目(No 30901810) （No 30901810）
广东省自然科学基金资助项目(No 9151503102000013) （No 9151503102000013）
