SIRT1在小鼠肝纤维化中的作用及转录差异基因分析  

Role of SIRT1 in Mouse Liver Fibrosis and Transcriptional Differential Genes Analysis

作　　者：冯文强[1] 张松[1] 丁美玲[1] 曹海超 聂勇战[1] 

机构地区：[1]第四军医大学西京消化病医院肿瘤生物学国家重点实验室,陕西西安710032

出　　处：《现代生物医学进展》2015年第9期1608-1612,1631,共6页Progress in Modern Biomedicine

基　　金：科技部重大国际合作项目(81110200);肝脏脂质代谢障碍中SIRT1相关分子的组学研究

摘　　要：目的:观察肝脏特异性SIRT1敲除(SIRT1-LKO)小鼠在四氯化碳(CCL4)诱导下的肝纤维化情况,系统地探讨SIRT1及转录差异基因在肝纤维化中的作用和机制。方法:利用Cre-Lox P重组酶系统构建SIRT1-LKO小鼠模型,经腹腔注射CCL4橄榄油溶液来诱导小鼠肝纤维化,通过血清生化检测肝功能,使用天狼星红染色观察肝脏胶原蛋白沉积,检测α-平滑肌肌动蛋白(α-SMA)的表达来观察肝星状细胞(HSCs)的活化,并进一步利用基因芯片技术和生物信息学分析来筛选转录差异基因。结果:在CCL4诱导下,SIRT1-LKO小鼠比同窝野生(WT)小鼠的肝损伤更加严重,肝纤维化也更为显著(P<0.05);通过对转录差异基因进行GO生物过程和KEGG通路分析,发现了一组可能与SIRT1和肝纤维化都存在相关的关键基因(TNC、TPM1、E2F1、DEFB1、LRTM1)。结论:SIRT1缺失会增加CCL4诱导的小鼠肝损伤,加重肝纤维化;SIRT1可能与上述基因协同参与了肝纤维化的发生发展。Objective： To observe liver fibrosis induced by carbon tetrachloride（CCl4） of liver-specific knockout of SIRT1（SIRT1-LKO） mice, and explore the role and mechanism of SIRT1 and transcriptional differential genes in the pathologic process of liver fibrosis systematically. Methods： SIRT1-LKO mice model was established by using a Cre-lox P approach. Liver fibrosis was induced by repetitive intraperitoneal CCl4 injection. Liver function was tested by serum biochemistry. Sirius red staining was used to observe the collagen accumulation. The α-smooth muscle actin（ α-SMA） immunohistochemistry was performed to show the hepatic stellate cells（HSCs） activation. The c DNA microarray technology and bioinformatics analysis were performed to screen transcriptional differential genes. Results： SIRT1-LKO mice had more serious liver injury and fibrosis than littermate WT mice after CCl4treatment（P〈0.05）. Some key differential genes（including TNC, TPM1, E2F1, DEFB1, LRTM1） were discovered through GO（Gene Ontology） biological process and KEGG（Kyoto Encyclopedia of Genes and Genomes） pathway analysis, which may be related with SIRT1 and liver fibrosis jointly.Conclusions： The deletion of SIRT1 enhanced liver injury and promoted liver fibrosis induced by CCl4 in mice. SIRT1 may cooperate with these genes and involve in the occurrence and development of liver fibrosis.

关 键 词：SIRT1 肝纤维化 基因芯片 生物信息学 

分 类 号：Q95-3[生物学—动物学] R575.2[医药卫生—消化系统]