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目的从基因转录水平了解急性肝衰竭(AHF)发生的基因组学基础。方法 36只SD成年大鼠分为模型组和对照组,模型组采用CCl4(4ml/kg)一次性灌胃法建立大鼠AHF模型,于建模3、6、12、24、48和72h时采集血清,检测谷丙转氨酶(ALT)、谷草转氨酶(AST)、碱性磷酸酶(ALP)、总蛋白(TP)、总胆红素(TBIL)等生化指标,并固定肝脏组织制作成石蜡切片,进行HE染色分析。用大鼠Genome 230 2.0芯片检测上述时间点肝脏细胞的基因表达谱,用系统生物学方法分析基因表达谱预示的生理活动。结果发现1 022个基因与大鼠AHF发生相关。其中,建模3、6、12、24、48、72h时有意义表达的基因数分别为131、302、350、539、349、177,有意义表达上调、下调和上下调的基因总数分别为634、382和6。用生物信息学和系统生物学等方法分析肝脏细胞基因表达谱与AHF发生的相关性,结果表明,AHF发生共涉及23种生理活动变化。其中,基因转录、糖类、脂类等代谢、内环境稳定、细胞增殖、生长、建成、迁移等8种生理活动增强。信号转导、核酸、有机酸、毒物等代谢、氧化还原、细胞黏附等6种生理活动减弱。炎症反应、细胞分化、发育等生理活动在AHF发生前期增强,后期减弱。结论 AHF发生与多种基因表达变化和多种生理活动改变密切相关。
Objective To understand the genomic basis of acute hepatic failure (AHF) from the gene transcriptional level. Methods Thirty-six adult SD rats were divided into model group and control group. The rats in model group were given intragastric administration of CCl4 (4ml / kg) once a day to establish AHF model. At 3, 6, 12, 24, 48 and 72h, The serum was collected and the biochemical indexes such as ALT, AST, ALP, TP and TBIL were detected, and the liver tissues were fixed to make paraffin sections , HE staining analysis. The rat Genome 230 2.0 chip was used to detect the gene expression profile of the liver cells at the above time points and the biological activity predicted by gene expression profile was analyzed by the method of systematic biology. The results found that 1 022 genes associated with the occurrence of rat AHF. Among them, there were 131,302,350,539,349,177 genes with significant expression at 3,6,12,24,48,72h, respectively. The total number of genes with up-regulated, down-regulated and down-regulated were 634,382 and 6. The correlation between gene expression profile of liver cells and occurrence of AHF was analyzed by bioinformatics and system biology methods. The results showed that there were 23 physiological activities involved in the development of AHF. Among them, eight kinds of physiological activities such as gene transcription, metabolism of carbohydrate and lipid, stable internal environment, cell proliferation, growth, completion and migration were enhanced. Signal transduction, nucleic acid, organic acids, toxins and other metabolic, redox, cell adhesion 6 kinds of physiological activity weakened. The inflammatory reaction, cell differentiation, development and other physiological activities in the pre-AHF increased, late weakened. Conclusion The occurrence of AHF is closely related to the changes of many genes and the changes of many physiological activities.