肝纤维化逆转中MAPK/ERK信号转导通路的活化及其特征  

Activation and characteristics of MAPK/ERK signal pathway during spontaneous resolution of hepatic fibrosis

作　　者：潘勤[1] 谢渭芬[2] 张忠兵[2] 张新 韩泽广 

机构地区：[1]上海第二医科大学附属新华医院消化内科,上海200092 [2]第二军医大学附属长征医院消化内科,上海200003 [3]国家人类基因组南方研究中心,上海201203

出　　处：《中国现代医学杂志》2006年第15期2253-2256,2260,共5页China Journal of Modern Medicine

基　　金：中国博士后科学基金资助项目(No:2004036325)

摘　　要：目的探讨有丝分裂原活化蛋白激酶(mitogen-activatedproteinkinase,MAPK)/细胞外信号调节激酶(extracellularsignal-regulatedproteinkinase,ERK)信号转导通路与肝纤维化自发逆转的相关性。方法采用CCl4注射SD大鼠8周,随后停药6周建立肝纤维化自发逆转的动物模型。采用cDNA微阵列杂交检测纤维化消退期间MAPK/ERK级联反应中有丝分裂原活化的蛋白激酶激酶激酶(mitogen-activatedproteinkinasekinasekinase,MAPKKK)、MAPKK、MAPK等上下游激酶的表达变化。并通过Northern杂交加以验证。结果肝纤维化自发逆转过程中,H-ras、A-raf、MAPKK2、ERK1及核糖体S6蛋白激酶(S6proteinkinase,RSK1)等MAPK/ERK信号转导通路中的关键激酶表达水平均显著提高,并呈现顺序激活的时序关系,ras抑制物的转录则明显下调。结论MAPK/ERK信号通路在肝纤维化消退时明显活化,可能与纤维化的自发逆转密切相关。[Objective] To investigate the relationship of MAPK/ERK signal pathway and the autoreversibility of hepatic fibrosis. [Methods] Animal model of hepatic fibrosis autoreversibility was established by CC14 exposure for 8 weeks and then withdraw for 6 weeks. The MAPK/ERK cascade, thereafter, was detected by cDNA microarray hybridization and verified by northern blot during the resolution of hepatic ftbrosis. [Results] Critical members of MAPK/ERK signal pathway including H-ras, A-raf, mitogen-activated protein kinase kinase 2 （MAPKK2）, extracellular signal-regulated protein kinase 1 （ERK1）, and S6 protein kinase （RSK1） exhibited greatly up-regulated expression levels, which were proved to reach the peak successively, throughout the hepatic fibrosis recovery. Contrastively, the mRNA level of ras inhibitor was significantly decreased. [Conclusion] The activation of MAPK/ERK signaling may play an important role in the hepatic fibrosis autoreversibility.

关 键 词：有丝分裂原活化蛋白激酶 细胞外信号调节激酶 信号通路 肝纤维化 逆转 

分 类 号：R-332[医药卫生]