肝纤维化自发逆转的相关信号转导通路研究  

Analysis of signal transduction pathways involved in spontaneous reversibility of hepatic fibrosis

作　　者：潘勤[1] 谢渭芬[2] 张忠兵[2] 

机构地区：[1]同济大学附属同济医院医学遗传研究所,上海200065 [2]第二军医大学附属长征医院消化内科,上海200003

出　　处：《中国现代医学杂志》2008年第4期446-449,453,共5页China Journal of Modern Medicine

基　　金：中国博士后科学基金资助项目(项目编号2004036325)

摘　　要：目的探讨肝纤维化自发逆转过程中不同信号转导通路的改变。方法通过四氯化碳(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、逆转录-聚合酶链式反应(RT-PCR)等检测多种信号通路成员的表达变化。结果除MAPK/EKR信号通路外,与肝纤维化自发逆转相关的差异表达基因属于数条信号转导通路,包括:SAPK/JNK信号通路中的SAPKβ、JunB原癌基因、JunD原癌基因、p53;MEK5信号通路中的MAPKK5;PI3K/Akt信号通路中的1,4,5-三磷酸肌醇3-激酶、1,4,5-三磷酸肌醇3-激酶B、HSP90 β、v-akt;Notch信号通路中的PS2。针对SAPK β、MAPKK5、1,4,5-三磷酸肌醇3-激酶及PS2的RT-PCR检测,结果与cDNA微阵列杂交相吻合。SAPK/JNK及Notch信号通路中的关键基因表达降低,MEK5、PI3K/Akt信号通路中的核心激酶表达水平上升,均可能促进肝细胞增殖、抑制其凋亡,从而诱导肝纤维化逆转。结论SAPK/JNK、MEK5、PI3K/Akt及Notch信号通路可能通过协同效应,在肝纤维化的自发逆转过程中发挥重要作用。[Objective] To investigate the signal transduction pathways involved in the spontaneous reversibility of hepatic fibrosis. [Methods] Hepatic fibrosis reversibility was established in SD rats by CCI4 administration for 8 weeks and then withdraw for 6 weeks. Thereafter, members of different signal pathways were detected by cDNA hybridization and verified by reverse transcription polymerase chain reaction （RT-PCR）. [Results] Besides MAPK/ ERK signal pathway, differentially expressed genes relevant to hepatic fibrosis reversibility were included in four signal pathways, including： SAPKβ, Jun B, Jun D and p53 of SAPK/JNK signal pathway; MAPKK5 of MEK5 signal pathway; Inositol 1,4,5-triphosphate 3-kinase, Inositol 1,4,5-trisphosphate, HSP9013 and v-akt of PI3K/Akt signal pathway; PS2 of Notch signal pathway. RT-PCR for SAPKβ, MAPKK5, inositol 1,4,5-triphosphate 3-kinase and PS2 also confirmed the results of cDNA hybridization. Both the down-regulated signal pathways （SAPK/JNK and Notch） and the up-regulated signal pathways （MEK5 and P13K/Akt） enhanced the proliferation of hepatocytes and inhibited their apoptosis. As a result, the resolution of hepatic fibrosis was induced. [Conclusion] The cooperative effects of different signal pathways, including SAPK/JNK, MEK5, P13K/Akt and Notch, may play a pivotal role in the spontaneous reversibility of hepatic fibrosis.

关 键 词：肝纤维化 逆转 信号转导通路 

分 类 号：R-332[医药卫生]