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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。
Objective To understand the correlation between cirrhosis (LC) and liver regeneration (LR). Methods Twenty-four adult male Sprague Dawley rats were used in this study. Six rats in each group were induced by CCl4 induction. 114 SD male rats were randomly divided into nine groups, including nine partial hepatectomy groups and nine sham operation Group and a normal control group. The LR model was established by 2/3 liver resection. Genome 230 2.0 was used to detect the gene expression profile of LC in rats and LR in rat liver. The similarities and differences in physiological activities predicted by gene expression profile were analyzed by bioinformatics and system biology methods. Quantitative PCR to prove the reliability of the chip test results. Results There were significant changes in 304 genes in LR and 948 genes in LR, of which 121 genes were common, 183 genes were LC-specific and 827 genes were LR-specific. H-clustering analysis showed that the physiological activities of LC and LR showed no temporal correlation. K-means clustering analysis showed that the expression trends of C1-C5 group in LC and LR were similar, but in C6 group, the change of LR was more abundant. Using gene ontology (GO) classification and functional clustering analysis, it was found that in LC and LR, the physiological activities such as immune response, inflammatory reaction, cell migration and cell adhesion increased, and the metabolism activity of various substances decreased. Among them, the stimulation of LC was stronger than that of liver regeneration at C2 and weaker than that of liver regeneration at C6, while DNA repair, cell proliferation, lipid metabolism, homeostasis and oxidative stress were all weaker than liver regeneration. Conclusion LC and LR gene expression changes and physiological activities have common, there are differences.