细胞外信号调节激酶对肝纤维化逆转的影响及其机制  

Effect of extracellular signal-regulated protein on hepatic fibrosis autoreversibility and its mechanism

作　　者：潘勤[1] 谢渭芬[1] 张忠兵[1] 张新 韩泽广 

机构地区：[1]第二军医大学长征医院消化内科,上海200003 [2]国家人类基因组南方研究中心,上海201203

出　　处：《第二军医大学学报》2005年第9期988-991,共4页Academic Journal of Second Military Medical University

基　　金：国家自然科学基金(30270604)

摘　　要：目的:探讨细胞外信号调节激酶(extracellular signal-regulated protein kinase,ERK)活化对肝纤维化自发逆转的影响及其作用机制。方法: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Northern杂交、免疫组化染色等检测ERK在纤维化消退过程中的活化状况、表达时序及在肝组织中的定位,并以cDNA微阵列杂交、RT-PCR等检测多种ERK底物在RNA、蛋白质水平的表达变化。结果:肝纤维化自发逆转过程中ERK表达水平显著提高,且由肝星状细胞(HSC)核表达为主转变为肝细胞胞质表达为主,多定位于小叶内、窦周间隙及纤维条索周围。核糖体S6蛋白激酶(RSK1)、c-fos、磷脂酶A2(PLA2)、离子通道及水通道、胃肠激素受体等ERK的下游基因转录也明显上调。结论:ERK与肝纤维化的自发逆转密切相关,可能通过多途径发挥保护肝细胞功能、促进肝细胞增殖、加速HSC凋亡等作用。Objective：To investigate the effect of extracellular signal-regulated protein kinase （ERK） on hepatic fibrosis autoreversibility and its mechanism. Methods： Animal model of hepatic fibrosis autoreversibility was established 6 weeks after 8 week CCl4 exposure. Then the activation, expression and distribution of ERK in the liver were investigated by Northern blot and immunohistochemistry during fibrosis reverse. RT-PCR and cDNA hybridization were used to detect the RNA and protein expression of ERK substrates. Results： The transcription of ERK was highly activated throughout the hepatic fibrosis recovery. ERK was located in the nucleus of hepatic stellate cells （HSCs） in fibrotic liver while it was mainly expressed in the hepatocyte cytoplasm of the lobule, sinusoid space, and perifibrous tissue as hepatic fibrosis resolved. Downstream molecules of ERK like S6 protein kinase （RSK1）, c-fos, phospholipase A2, ion channels, and gastrointestinal hormone receptors were also found up regulated during the whole course. Conclusion： ERK may be closely related to hepatic fibrosis reversibility and it may protect and promote proliferation of hepatocyte and induce apoptosis of HSC.

关 键 词：细胞外信号调节激酶 肝纤维化 逆转 

分 类 号：R575.2[医药卫生—消化系统]