钙调神经磷酸酶介导碱性成纤维细胞生长因子诱导的大鼠心肌细胞肥大  

Role of calcineurin in signal transduction of bFGF-induced cardiac myocyte hypertrophy of rats

作　　者：符民桂[1] 许松[2] 庞永正[1] 刘乃奎[1] 唐朝枢[1] 

机构地区：[1]北京大学第一医院心血管病研究所,北京100034 [2]北京大学第一医院中心实验室,北京100034

出　　处：《北京大学学报（医学版）》2001年第1期38-41,共4页Journal of Peking University:Health Sciences

基　　金：国家自然科学基金重点项目! ( 39730 2 2 0 &&

摘　　要：目的 :观察钙调神经磷酸酶 (calcineurin ,CaN)在碱性成纤维细胞生长因子 (basicfibroblastgrowthfactor,bFGF)诱导心肌细胞肥大中的作用。方法 :在原代培养的大鼠心肌细胞上 ,应用双波长荧光光度计检测心肌细胞游离Ca2 +浓度 ;应用对硝基苯磷酸 (p nitrophenylphosphate,PNPP)作底物测定CaN活性 ;根据3H 亮氨酸参入水平评估各种信号通路阻断剂对bFGF刺激的心肌细胞蛋白质合成速率的影响。结果 :bFGF刺激心肌细胞 2 4h后 ,胞内游离Ca2 +浓度较对照组增高 2 72 % (P <0 .0 1) ;同时 ,bFGF刺激的心肌细胞CaN活性较对照组增高 173 %(P <0 .0 1)。bFGF( 6 0 μg·L-1)刺激的心肌细胞3H 亮氨酸参入较对照组增高 10 6 % (P <0 .0 1) ;CsA( 0 .1～ 10 μmol·L-1)可以浓度依赖的方式抑制bFGF刺激的心肌细胞3H 亮氨酸参入。此外H7(PKC抑制剂 )和 5 0 μmol·L-1PD980 59(MAPK抑制剂 )亦可完全阻断bFGF刺激的心肌细胞3H 亮氨酸参入。结论 :Ca2 +/CaN信号通路参与bFGF诱导心肌细胞肥大的信息传递。另外 。Objective: To investigate the role of calcineurin in signal transduction of bFGF induced cardiac myocyte hypertrophy of rats. Methods: [Ca 2+ ] i and calcineurin activity in primary cultured rat cardiomyocytes were tested. The effect of various inhibitors on protein synthesis rate in bFGF stimulated cardiomyocytes were estimated by 3H Leucine incorporation. Results: 24 h after treated with bFGF, [Ca 2+ ] i and calcineurin activity in cardiomyocytes were increased by 272% and 173%( P < 0.01 ) respectively, compared with that in the control group. The 3H Leucine incorporation in bFGF stimulated myocytes was increased by 106%( P <0.01), which was inhibited by CsA(0.1～10 μmol·L -1 ) in a dose dependent manner. In addition, it was shown that PD 98059 and H 7 (50 μmol·L -1 ) could completely block the increase of 3H Leucine incorporation in bFGF stimulated cardiomyocytes of rats. Conclusion: Ca 2+ /Calcineurin dependent signal pathway may involve in the bFGF induced cardiac myocyte hypertrophy. MAPK (mitogen activated protein kinase) and PKC (protein kinase C) may also play an important role in the signal transduction of bFGF induced cardiomyocyte hypertrophy.

关 键 词：碱性成纤维细胞生长因子 心肌细胞肥大 信号传递 钙调神经磷酸酶 

分 类 号：R542.2[医药卫生—心血管疾病]