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目的从基因转录水平了解JNK信号通路在大鼠肝再生(LR)和肝硬化(LC)中的作用异同。方法采用2/3部分肝切除手术制备大鼠肝再生模型,以腹腔注射CCl4中性菜籽油溶液法建立大鼠肝硬化模型,采用大鼠Genome 230 2.0芯片检测不同时间点再生肝和肝硬化组织中JNK信号通路的基因表达谱,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增殖和凋亡活动。结果 JNK信号通路涉及302个基因和42条途径,大鼠Genome 230 2.0芯片含上述基因中的240个基因,其中,79个基因发生有意义表达变化,涉及LR的52个基因,LC的5个基因,有22个基因与两者相关。在大鼠LR启动阶段,途径1和16促进细胞增殖及途径22～33促进细胞凋亡作用强于对照;在进展阶段,途径1～17、34和35促进细胞增殖及途径22～33促进细胞凋亡作用强于对照,途径37～41抑制细胞凋亡作用弱于对照;在终止阶段,途径37、39、41和42诱导细胞凋亡作用弱于对照,同时,尚未发现途径18～21和36参与大鼠LR。而在LC发生中,JNK信号通路中的这些途径与对照相比均无显著差异。结论 JNK信号通路的37条途径调控大鼠肝再生的细胞增殖和凋亡,对大鼠肝硬化的调控作用则不显著。
Objective To investigate the role of JNK signaling pathway in rat liver regeneration (LR) and cirrhosis (LC) from the gene transcriptional level. Methods Two-thirds partial hepatectomy was used to prepare the rat model of liver regeneration. Rat model of hepatic cirrhosis was established by intraperitoneal injection of CCl4 neutral rapeseed oil solution. Genome 230 2.0 was used to detect liver regeneration and cirrhosis at different time points The gene expression profiles of JNK signaling pathways in tissues were analyzed by bioinformatics and system biology methods to predict the proliferation and apoptosis events predicted by gene expression profiling. Results The JNK signaling pathway involved 302 genes and 42 pathways. The rat Genome 230 2.0 chip contained 240 of the above genes, of which 79 genes had significant changes, involving 52 LR genes and 5 LC Gene, 22 genes associated with both. Pathways 1 and 16 promote cell proliferation and pathways 22-33 promote cell apoptosis in the rat LR-primed phase, while in the progression stage, pathways 1 to 17, 34 and 35 promote cell proliferation and pathways 22 to 33 promote cells Apoptosis was stronger than that of the control. Pathway 37-41 inhibited cell apoptosis less than control. At the termination stage, pathways 37, 39, 41 and 42 induced apoptosis less than control. At the same time, pathways 18-21 and 36 participates in rat LR. However, in LC, these pathways in JNK signaling pathway were not significantly different from the control. Conclusion 37 pathways of JNK signaling pathway regulate the proliferation and apoptosis of rat liver regenerated cells and have no significant effect on the regulation of liver cirrhosis in rats.