张玉珍, 朱鼎良, 高平进, 王兴宇, Marche, P, 张宗梁. 氨氯地平抑制人血管平滑肌细胞增殖机制的研究J. 药学学报, 2000, 35(9): 645-648.
引用本文: 张玉珍, 朱鼎良, 高平进, 王兴宇, Marche, P, 张宗梁. 氨氯地平抑制人血管平滑肌细胞增殖机制的研究J. 药学学报, 2000, 35(9): 645-648.
ZHANG Yu-zhen ZHU Ding-liang GAO Ping-jin, WANG Xing-yu ZHANG Zong-liang, Marche Pierre, . THE MECHANISMS OF INHIBITION OF AMLODIPINE ON HUMAN VASCULAR SMOOTH MUSCLE CELL PROLIFERATIONJ. Acta Pharmaceutica Sinica, 2000, 35(9): 645-648.
Citation: ZHANG Yu-zhen ZHU Ding-liang GAO Ping-jin, WANG Xing-yu ZHANG Zong-liang, Marche Pierre, . THE MECHANISMS OF INHIBITION OF AMLODIPINE ON HUMAN VASCULAR SMOOTH MUSCLE CELL PROLIFERATIONJ. Acta Pharmaceutica Sinica, 2000, 35(9): 645-648.

氨氯地平抑制人血管平滑肌细胞增殖机制的研究

THE MECHANISMS OF INHIBITION OF AMLODIPINE ON HUMAN VASCULAR SMOOTH MUSCLE CELL PROLIFERATION

  • 摘要: 目的 观察氨氯地平对人血管平滑肌细胞(VSMC)丝裂素活化蛋白激酶(MAPK)活性的影响。方法 取人乳腺下动脉培养VSMC,用bFGF刺激细胞增殖,观察氨氯地平对bFGF激活的MAPK活性的影响,用p42/p44磷酸化抗体蛋白免疫印迹法测定MAPK活性。 结果 bFGF对MAPK有显著激活作用,激活峰值出现在5~15 min,维持至3 h; 此活化作用被MAPK激酶的特异抑制剂PD98059抑制; 无论瞬时或持久的bFGF激活的MAPK活性均被氨氯地平抑制。 结论 氨氯地平通过MAPK信号转导途径抑制bFGF所致的细胞增殖。

     

    Abstract: AIM Mitogen-activated protein kinase (MAPK) plays an important role on growth factor-induced cell growth and proliferation. This study was designed to determine whether MAPK is involved in the inhibitory effect of amlodipine on basic fibroblast growth factor (bFGF)-induced vascular smooth muscle cell (VSMC) proliferation. METHODS Human VSMC were obtained from lower mammary artery. MAPK activity was measured by immunobloting using anti-p42/p44 phospho-MAPK antibody. RESULTS bFGF (20 ng.mL-1) significantly activated MAPK with a peak time at 5~15 min, maintained for 3 h. PD98059 (0.1~10 μmol.L-1), a specific inhibitor of MAPK kinase, inhibited bFGF-induced MAPK activation in a dose-dependent manner. Amlodipine (1~100 nmol.L-1) dose-dependently inhibited MAPK activation by bFGF. Amlodipine (10 nmol.L-1) was shown to inhibit both short-term and long-term MAPK activation induced by bFGF. CONCLUSION The results indicated that bFGF could significantly activate MAPK. Amlodipine, which could inhibit bFGF-induced human VSMC proliferation, inhibit both short-term and sustained MAPK activation by bFGF. It is suggested that bFGF-induced VSMC proliferation may be related to MAPK activation, and the antiproliferation effect of amlodipine may be related to its inhibition of MAPK activation.

     

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