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异丙肾上腺素对小鼠心肌MAPK、NF#kappa#B和JAK/STAT信号转导途径的激活效应

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,该工作以成年雄性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-#kappa#B(NF#kappa#B)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(5min)激活心肌MAPK(ERK1/2和p38);ISO对心肌NF#kappa#B的激活效应表现为双相性,激活高峰分别为5和120min;ISO腹腔注射60min后可显著促进STAT3的酪氨酸磷酸化,6h时基本恢复到基础水平。上述结果显示,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

Isoproterenol-induced activation of MAPK, NF#kappa#B and JAK/STAT pathway in mouse myocardium

Yin Feng, Zhu Yun, Li Ping, Han Qide, Zhang Youyi

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 mitogen-activted protein kinase (MAPK), NF-#kappa#B and JAK/STAT pathway in the left ventricular myocardium was measured by Western blot analysis. ISO significantly activated MAPK (ERK1/2 and p38) at early phase (5 min); biphasic activation of NF-#kappa#B was observed in our in vivo study; and ISO caused a delayed STAT3 activation (at 60 to 240 min) in mouse myocardium. Taken together, these results indicate that ISO activates these signal transduction pathways in different time course.

Key words: Isoproterenol;Myocardium;Mitogen-activted;Protein kinase （MAPK）;NFKB JAK/STAT

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引用本文：

尹峰, 朱昀, 李平, 韩启德, 张幼怡. 异丙肾上腺素对小鼠心肌MAPK、NF#kappa#B和JAK/STAT信号转导途径的激活效应[J]. 生理学报 2003; 55 (4): .

Yin Feng, Zhu Yun, Li Ping, Han Qide, Zhang Youyi. Isoproterenol-induced activation of MAPK, NF#kappa#B and JAK/STAT pathway in mouse myocardium. Acta Physiol Sin 2003; 55 (4): (in Chinese with English abstract).