论文部分内容阅读
以四氯化碳(Carbon tetrachloride,CCl4)诱导小鼠肝组织纤维化为研究模型,发现并探讨纤维化肝组织与正常肝组织在蛋白质组水平上的差异。实验小鼠(C57 BL/6)随机分为两组,由橄榄油和四氯化碳诱导15周,并分别对这两组肝组织的全蛋白表达谱进行质谱检测,应用GO(Gene Ontology)功能分类分析和KEGG(Kyoto Enyoolpedia of Genes and Genomes)信号通路的富集分析方法对鉴定到的全蛋白表达谱进行差异表达分析。在对照组和实验组中,我们分别鉴定到17 382和20 486条特异性肽段,图谱平均利用率大于50%,共计鉴定到蛋白4 991种(蛋白特异性肽段个数至少为1),其中差异表达蛋白有2 135种(差异倍数大于或等于2),表达上调蛋白1 264种,下调蛋白871种。纤维化肝脏组织中与细胞外基质组成(Extracellular matrix organization)、细胞骨架组成(Cytoskeleton organization)、有机磷酸代谢(Organophosphate metabolic process)、细胞定位(Cellular localization)和细胞组分调节(Regulation of cellular component organization)相关蛋白的表达是上调的;另外,与小分子代谢(Small molecule metabolic process)、蛋白质转运(Protein transport)和有机氮化合物的代谢(Organonitrogen compound metabolic process),以及四吡咯的合成过程(Tetrapyrrole biosynthetic process)有关蛋白的表达是下调的。信号通路富集分析结果表明,纤维化与VEGF和T细胞受体信号调节通路密切相关。结果提示,纤维化的形成不仅是一个复杂的信号转导过程,更是一个炎症与免疫相互促成的结果;增强肝实质细胞的存活,降低相关信号的传递及接收都有可能对纤维化的发生和发展起到抑制效果。
Carbon tetrachloride (CCl4) -induced hepatic fibrosis in mice as a model to find and explore the difference between the proteome level of fibrotic liver tissue and normal liver tissue. The experimental mice (C57 BL / 6) were randomly divided into two groups and were induced by olive oil and carbon tetrachloride for 15 weeks. The whole protein expression profiles of the two groups of liver tissues were detected by mass spectrometry. GO (Gene Ontology) Functional analysis and Enrichment of KEGG (Kyoto Encyclopedia of Genes and Genomes) signal pathway enrichment analysis of the differential expression analysis of the identified whole protein expression profile. In the control group and the experimental group, we identified 17 382 and 20 486 specific peptides, the average utilization rate of more than 50%, a total of 4 991 proteins were identified (the number of protein-specific peptides is at least 1) , Of which there were 2 135 differentially expressed proteins (with a difference multiple of 2 or more), 1 264 species of up-regulated proteins and 871 proteins of down-regulated proteins. Extracellular matrix organization, Cytoskeleton organization, Organophosphate metabolic process, Cellular localization and Regulation of cellular component organization in fibrosis liver tissues. ) Protein is up-regulated. In addition, it is associated with Small molecule metabolic process, Protein transport and Organonitrogen compound metabolic process, and Tetrapyrrole biosynthesis The protein expression is downregulated. Enrichment analysis of signal pathways showed that fibrosis is closely related to the signal transduction pathways of VEGF and T cell receptors. The results suggest that the formation of fibrosis is not only a complex signal transduction process, but also a result of the mutual promotion of inflammation and immunity; enhance the survival of hepatic parenchymal cells, reduce the transmission and receipt of relevant signals are likely to occur on fibrosis And development has played a inhibitory effect.