基础医学与临床 ›› 2009, Vol. 29 ›› Issue (10): 1087-1091.

• 研究论文 • 上一篇    下一篇

CaN-NFAT信号通路参与苯肾上腺素介导的血管平滑肌细胞增殖

庞晓 何培英 孙宁玲   

  1. 北京大学人民医院 北京大学人民医院 北京大学人民医院
  • 收稿日期:2008-11-24 修回日期:2009-01-14 出版日期:2009-10-20 发布日期:2009-10-20
  • 通讯作者: 孙宁玲

Calcineurin-NFAT pathway mediates phenylephrine-induced vascular smooth muscle cell proliferation

Xiao PANG, Pei-ying HE, Ning-ling SUN   

  1. People's Hospital, Peking University People's Hospital, Peking University
  • Received:2008-11-24 Revised:2009-01-14 Online:2009-10-20 Published:2009-10-20
  • Contact: Ning-ling SUN

摘要: 目的 研究钙调神经磷酸酶-活化T细胞核因子(CaN-NFAT)信号通路对苯肾上腺素诱导的血管平滑肌细胞(VSMCs)增殖的调节作用。方法:组织贴块法原代培养SD大鼠血管平滑肌细胞,MTT法和细胞计数法测定VSMCs增殖,间接免疫荧光法测定NFATc1细胞定位,Western blot测定CaN蛋白表达,定磷法检测CaN活性。结果:苯肾上腺素(PE,α1-受体激动剂)促进VSMCs增殖,哌唑嗪(prazosin,α1-受体抑制剂)和环胞霉素A(CsA,CaN抑制剂)降低PE诱发的VSMCs增殖,白屈菜红碱(chelerythrine,蛋白激酶C抑制剂)预处理VSMCs后,PE诱发的VSMCs吸光度和细胞数被抑制, 并且这种抑制作用可以被CsA进一步加强。CsA抑制PE诱发的CaN表达与活性。PE促进NFATc1从胞质易位入核,CsA抑制NFATc1核转位。结论:CaN-NFATc1信号通路参与调节苯肾上腺素诱导的VSMCs增生肥大。

关键词: 儿茶酚胺, 钙调神经磷酸酶, 活化T细胞核因子, 增殖, 血管平滑肌细胞

Abstract: Objective To determine whether calcineurin-NFAT pathway is involved in the regulation of VSMCs proliferation induced by catecholamines. Methods Primary VSMCs from rat aorta were used as the experimental model. Proliferation of VSMCs were measured by MTT assay and cell count. Calcineurin protein and its activity were assayed using immunoblotting and free inorganic phosphate content analysis respectively. Localization of NFATc1 was detected by immunofluorescence staining. Results Phenylephrine (PE, an α1-adrenoceptor agonist) increased VSMCs proliferation. Prazosin (an α1-adrenoceptor antagonist), cyclosporin A (CsA, an inhibitor of calcineurin) and chelerythrine (an inhibitor of PKC) decreased PE-induced absorbance and cell number. Timolol (β-adrenoceptor antagonist) has no effect on absorbance and cell number induced by PE. Additional treatment with CsA further inhibited PE-induced absorbance and cell number compared with the chelerythrine pretreatment group. CsA and chelerythrine alone had no significant effect on either absorbance or cell number. CsA decresed PE-induced calcineurin level and its activity. NFATc1 was translocated from cytoplasm to nucleus upon treatment with PE. This translocation was reversed by CsA. Conclusions CsA partially inhibits PE-induced VSMCs proliferation via inhibiting calcineurin activity and NFATc1 nuclear translocation. Calcineurin-NFATc1 pathway is involved in hyperplastic growth of VSMCs induced by catecholamines.

Key words: catecholamines, calcineurin, nuclear factor of activated T cells, proliferation, vascular smooth muscle cells