全基因表达谱分析维甲酸对大鼠肝纤维化的影响  

Whole genome analysis of the effect of retinoic acid on liver fibrosis

作　　者：喻冬柯[1] 高塬[1] 张彩霞[1] 张胜华[1] 甄永占[2] 邵荣光[1] 何红伟[1] 

机构地区：[1]中国医学科学院北京协和医学院医药生物技术研究所,北京100050 [2]河北联合大学基础医学院,河北唐山063000

出　　处：《中国药理学通报》2013年第9期1213-1216,共4页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81170409);中国肝炎防治基金会-王宝恩肝纤维化研究基金资助课题(No20110026);国家重点基础研究发展计划(973计划)资助项目(No 2009CB521807);国家"重大新药创制"科技重大专项(No 2012ZX09301002-001)

摘　　要：目的探讨维甲酸对胆管结扎肝纤维化模型大鼠肝脏组织全基因表达谱的影响。方法应用维甲酸给予胆管结扎大鼠模型,用大鼠全基因芯片分析肝组织基因表达谱,并进行通路分析,实时定量PCR和Western blot分析与验证肝纤维化相关基因的表达变化。结果全基因组芯片分析表明:共有491个基因同时在模型组和维甲酸组中发生变化,该变化与细胞黏附、整合素等信号通路有关,并影响药物代谢,视黄醇代谢,淀粉、蔗糖和半乳糖代谢,脂代谢的相关信号通路。实时定量PCR检测结果显示,与模型组相比,维甲酸能抑制肝脏组织中肝纤维化相关基因(Col1a1和TGF-β)的mRNA水平,降低肝纤维化相关蛋白(TGF-β、α-SMA)的表达。结论维甲酸可以有效改善胆管结扎大鼠模型的肝纤维化的程度,逆转胆管结扎造成的基因表达变化,其中包括下调多种肝纤维化基因,从而发挥抗纤维化的作用。Aim To investigate the effects of retinoic acid on liver fibrosis induced by bile duct ligation in rats and to observe the variation of liver fibrosis genome before and after the treatment of retinoic acid. MethodsThe rat whole genome oligonucleotide microarray was used to analyze the gene expression profiling in the bile duct ligation rat model liver tissue. According to the results, the pathway analysis was taken. RT-PCR and Western blot were used to verify the expression of liver fibrosis related genes. Results Whole genome mi- croarray analysis showed that including a total of 491 genes changed in the two groups of treatment, these genes were related to cells adhesion and integrin signa- ling pathways, and affected drug metabolism, retinol metabolism, starch, sucrose and galactose metabolism, lipid metabolism pathway. RT-PCR analysis showed that compared with the model group, retinoic acid in- hibited the mRNA levels of liver fibrosis in liver tissue related gene （Coll al and Tgfβ）, of reducing the ex- pression of liver fibrosis-related protein （Tgfβ, α- Sma）. Conclusion Bile duct ligation markedly in- duces the changes of multiple metabolic pathways and signal transduction pathways in the liver. Retinoic acid could effectively repress the liver fibrosis level of bile duct ligation rats, and reverse the changes in gene ex- pression caused by bile duct ligation, including down- regulation of fibrosis related genes, which play the role of anti-fibrosis.

关 键 词：维甲酸 大鼠 胆管结扎 肝纤维化 信号通路 基因表达谱 基因芯片 

分 类 号：R-332[医药卫生] R322.47