异丙肾上腺素对小鼠心肌MAPK、NFκB和JAK/STAT信号传导途径的激活效应

尹峰, 朱昀, 李平, 韩启德, 张幼怡*

北京大学第三医院血管医学研究所, 分子心血管教育部重点实验室, 北京 100083

摘要: 为研究异丙肾上腺素(ISO)诱导心肌肥厚或心肌重塑的分子机制, 本工作以成年雄性Balb/c小鼠为研究对象, 通过腹腔注射ISO, 采用蛋白免疫印迹杂交方法观察ISO对小鼠心肌丝裂素活化蛋白激酶(MAPK)、核因子-κB (NFκB)和Janus激酶/信号转导因子和转录激活因子(JAK/STAT)途径的激活效应。结果发现, ISO腹腔注射后可早期(5 min)激活心肌MAPK (ERK1/2和p38); ISO对心肌NFκB的激活效应表现为双相性, 激活高峰分别为5和120 min; ISO腹腔注射60 min后可显著促进STAT3的酪氨酸磷酸化, 6 h时基本恢复到基础水平。上述结果提示, ISO对多种细胞内信号转导途径均具有激活效应, 但表现出明显的时相差异。探明这些信号转导途径的时空整合规律, 将有助于深化对心肌重塑发生机制的认识。

关键词: 异丙肾上腺素; 心肌; 丝裂素活化蛋白激酶; 核因子-κB; Janus激酶/信号转导因子和转录激活因子

中图分类号: Q463

Isoproterenol induced activation of MAPK, NFκB and JAK/STAT pathway in mouse myocardium

YIN Feng, ZHU Yun, LI Ping, HAN Qi-De, ZHANG You-Yi*

Institute of Vascular Medicine, Peking University Third Hospital, The Reference Laboratory of Education Ministry on Molecular Cardiology, Beijing 100083

Abstract: This study was aimed to determine the in vivo signal transduction pathway responsible for isoproterenol (ISO)-induced cardiac hypertrophy or remodeling. Mice were treated with ISO (15 mg/kg body weight) or vehicle by intraperitoneal injection (i.p.). Activation of MAPK, NF-κB and JAK/STAT pathway in left ventricular myocardium were measured by Western blot analysis. ISO significantly activated MAPK (ERK1/2 and p38) at early phase (5 min); Biphasic activation of NF-κB was observed in our in vivo study; ISO caused a delayed STAT3 activation (at 60 to 240 min) in mouse myocardium. Taken together, these results indicate that ISO activate these signal transduction pathways in different time course.

Key words: isoproterenol; myocardium; MAPK; NFκB; JAK/STAT