钙激动剂诱导心肌肥大转录因子的表达  

Calcium activator induced the expression of myocardium hypertrophy transcription factor

作　　者：杨永健[1] 速晓华[1] 李刚[1] 朱峻[1] 陈劲松[1] 周兴文[1] 

机构地区：[1]成都军区总医院心血管内科,四川成都610083

出　　处：《中国药理学通报》2005年第2期224-227,共4页Chinese Pharmacological Bulletin

摘　　要：目的　探讨不同来源的细胞内游离Ca2+ 浓度( [Ca2+ ] )在钙神经磷酸酶 (CaN) 活化T细胞核因子 3(NFAT3 )介导心肌肥大中的作用。方法　分别用血管紧张素Ⅱ(AngⅡ )或雷诺定 (RY)刺激培养的大鼠心肌细胞外Ca2+跨膜内流或细胞内Ca2+释放,检测CaN、NFAT3、锌指转录因子(GATA4 )蛋白量以及氚 亮氨酸 (3H Leu)参入量,环孢素A(CsA)作为CaN特异抑制剂。结果　AngⅡ、RY刺激1、3d,心肌细胞CaN、NFAT3、GATA4 蛋白表达及 3H Leu参入量较对照组明显增高 (P<0 05或 <0 01 )。CsA可抑制上述作用,与刺激组相比差异有显著性 (P< 0 05或 <0 01)。结论　刺激心肌细胞Ca2+内流及Ca2+释放,均可激活CaN NFAT3 信号通路。该信号通路的激活与 [Ca2+ ]i增加有关,而与[Ca2+ ]i的来源无关。CsA能够抑制AngⅡ和RY介导的CaN NFAT3 GATA4 表达的增加和蛋白质合成。Aim To investigate the role of [Ca 2+] i form different origins in the course of myocardial hypertrophy mediated by calcineurin (CaN)- nuclear activated T cell factor(NFAT 3) signal transduction.Methods The primarily cultured crdio myocyte were irritated with angiotensin(Ang) Ⅱ and ryanodine(RY) which Cause Ca 2+ inflow and release respectively. Then to observe the changes of (CaN)-NFAT 3 path way were then observed. Western blotting was employed to se mi-quantify CaN, NFAT 3 and zinic finger transcription factor(GATA 4). 3H-Leu incorporation was used as an index of myocyte hypertrophy. Cyclosporin A (CsA) was applied to restrain CaN-NFAT 3 pathway as a kind of CaN-selective antagonist.Results CaN, NFA T 3, GATA 4 expression significantly increased 1 and 3 days after the stimulation of cardiomyocytes with Ang Ⅱ and RY(10 -7 mol·L -1) as compared with that of a control group (P<0.05) and 3H-Leu incorporation distinctly increased after Ang Ⅱ and RY(10 -7 mol·L -1) stimulation (P<0.05) versus control group. On the first day of Ang Ⅱ and RY stimulation. All of the above effects were suppressed by CsA administration, but they were rarely suppressed if CsA was not administered (P<0.05). Conclusion It is shown that both Ca 2+ inflow and release may activate CaN-NFAT 3 signal pathway, which responds to increase of [Ca 2+] i and is independent of its origin, indicating the augment of [Ca 2+] i may trigger CaN-NFAT 3 signal transduction and consequently induce myocyte hypertrophy. More over, CsA may restrain the expression and activation of CaN-NFAT 3 and protein synthesis of myocytes in response to Ang Ⅱ and RY stimulation.

关 键 词：心肌肥大 转录因子 钙激动剂 

分 类 号：R-332[医药卫生] R322.11