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

目的探讨碘化N-正丁基氟哌啶醇(F2)对血管紧张素Ⅱ(AngII)诱导心肌细胞肥大的抑制作用及其机制。方法培养大鼠心肌细胞株(H9C2细胞),测量细胞表面积和BCA法测定细胞蛋白含量作为心肌肥大指标;Western blot检测核转录因子ERK1/2及CREB蛋白表达。结果 (1)AngII(10-7mol.L-1)处理细胞48 h,心肌细胞表面积增大,蛋白含量明显增加,F2(10-8、10-7、10-6mol.L-1)剂量依赖抑制AngII介导心肌细胞表面积的增大以及蛋白含量的增加;(2)AngII(10-7mol.L-1)处理心肌细胞1 min,磷酸化ERK1/2蛋白(p-ERK1/2)和磷酸化CREB蛋白(p-CREB)表达即开始增加,5～10 min达最高峰,可持续活化60 min,ERK1/2和CREB蛋白总量没有变化。以AngII处理心肌细胞5 min,p-ERK1/2和p-CREB表达为标准,预先以F2(10-8、10-7、10-6mol.L-1)处理心肌细胞30 min,F2剂量依赖抑制AngII介导心肌细胞p-ERK1/2和p-CREB表达的增高。结论 F2可以抑制AngII诱导的心肌肥大,其机制可能与抑制磷酸化ERK1/2和CREB表达有关。

Aim To investigate the effects of N-n-bu- tyl haloperidol iodide （F2 ） on angiotensin II （AngII）- induced cardiomyocyte hypertrophy and the mecha- nism. Methods In the cultured rat cardiomyocyte cell line （H9C2） , as indexes of cardiomyocyte hyper- trophy, the cell surface area of H9C2 cells was meas- ured and the total proteins of H9C2 cells were deter- mined by BCA method. The expression of the nuclear transcription factor, extraeellular 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 AngII （10-7mol L-1） with 48h in the cardiomyo- cytes of the H9C2 cells increased significantly in con- trast 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 AnglI in a dose-de- pendent manner. AngII 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 expres- sion 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-1） for 30 min, Ang Ⅱ-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 in- duced by AngII, and the mechanism might be associat- ed with its inhibitory effect on ERK and CREB.