关键词: 肝硬化, 肝再生, Genome 230 2.0芯片, 荧光定量PCR, 基因表达谱, 大鼠

Abstract: Objective To explore the relevance of rat liver cirrhosis (LC) to rat liver regeneration (LR). Methods The model of CCl4-induced LC was established by using 24 adult SD male rats (6 rats in each group). 114 adult SD male rats were randomly divided into 19 groups consisting of 9 partial hepatectomy groups, 9 sham operation groups and 1 normal control group, and 2/3 partial hepatectomy-induced LR was established. Then Rat Genome 230 2.0 array was used to detect gene expression profiles of livers tissues obtained from the above two models. Some methods of bioinformatics and systematic biology were applied to uncover the correlation of gene expression changes and physiological activities between the LC and LR. The reliability of the array data was confirmed by real-time polymerase chain reaction (RT-PCR). Results It was found that 304 genes were changed significantly in expression in rat LC occurrence and 948 genes in rat LR. Of them, 183 genes were the LC-specific, 827 genes were the LR-specific, and 121 genes were shared in both. H-clustering analysis demonstrated that physiological activities of LC had no correlation with those of LR in time. K-means cluster analysis revealed that gene expression trends of Cluster 1-5 (C1-5) groups were similar in LC and in LR, and that those of their C6 group were contrary with the gene expression changes of LR more abundant. Gene ontology(GO) classifications and functional cluster analysis found that physiological activities including immune and inflammatory response, cell migration and adhesion were increased both in LC and in LR, whereas various metabolic activities were decreased. Among them, reaction of liver to stimulation in LC was stronger than in LR in C 2, but in C 6 showed a contrary result. At the same time, DNA repair, cell proliferation, lipid metabolism, homeostasis, oxidation reduction etc in LC were weaker than in LR. BR>Conclusion The changes in gene expressions and physiological activities of LC and those of LR have not only similarities but also differences. BR>

Key words: Liver cirrhosis, Liver regeneration, Genome 230 2.0 array, Fluorescence quantitative PCR, Gene expression profile, Rat