大鼠肝硬化与肝再生的基因表达谱比较分析

目的 了解肝硬化(LC)与肝再生(LR)的相关性.方法 取成年SD雄性大鼠24只,每组6只,用CCl4诱导方法 建立大鼠LC模型;将114只SD雄性大鼠随机分为19组,包括9个部分肝切除组,9个假手术组和1个正常对照组,用2/3肝切除手术建立LR模型.用大鼠全基因组表达谱芯片Genome 230 2.0检测大鼠LC发生与大鼠LR中肝组织的基因表达谱,用生物信息学和系统生物学等方法 分析基因表达谱预示的生理活动的异同,并用定量PCR证明芯片检测结果 的可靠性.结果 LC发生中304个基因和LR中948个基因发生了有意义表达变化,其中121个基因为两者共有,183个基因为LC特有,827个基因为LR特有.H-clustering分析表明,LC和LR的生理活动未显示时间上的相关性.K-means聚类分析显示,LC和LR的C1～C5组基因表达趋势相似,C6组相反,但LR的变化更为丰富.应用基因本体论(GO)分类和功能聚类分析发现,在LC和LR中,免疫反应、炎症反应、细胞迁移、细胞黏附等生理活动增强,各种物质代谢活动减弱.其中,LC的刺激反应在C2强于肝再生,在C6弱于肝再生,而DNA修复、细胞增殖、脂类代谢、内环境稳态和氧化应激等均弱于肝再生.结论 LC与LR的基因表达变化和生理活动有共同方面,也有差异之处.

Comparative analysis of gene expression profiles between liver cirrhosis and liver regeneration in rats

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>