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

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

作　　者：尹峰[1] 朱昀[1] 李平[1] 韩启德[1] 张幼怡[1] 

机构地区：[1]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

出　　处：《生理学报》2003年第4期449-453,共5页Acta Physiologica Sinica

基　　金：This work was supported by the Major State Research Development Program of People's Republic of China (No. G2000056906);the National Science Foundation of China (No. 30070872).

摘　　要：为研究异丙肾上腺素(isoproterenol,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(mitogen-activted protein kinase,MAPK)、核因子-κB(NFKB)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,6h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。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 (15mg/kg body weight) or vehicle by intraperitoneal injection (i. p.). Activation of mitogen-activted protein kinase (MAPK), NF-κB 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-κB 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.

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 

分 类 号：Q463[生物学—生理学]