Differential gene expression profiles in the steatosis/fibrosis model of rat liver by chronic administration of carbon tetrachloride
Differential gene expression profiles in the steatosis/fibrosis model of rat liver by chronic administration of carbon tetrachloride
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DOI：
10.1016/j.taap.2005.03.002
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发表时间：
2005-11-01
影响因子：
3.8
通讯作者：
Kong, G
中科院分区：
文献类型：
--
作者：
Chung, H;Hong, DP;Kong, G
通过微阵列分析慢性四氯化碳（CCl 4）给药后大鼠肝脏RNA的整体基因表达谱进行了分析。大鼠每周三次接受0.5 MI CCl 4/kg，并在注射0、30、60和90天后采集肝脏样本。肝组织的组织病理学研究能够将CCl 4的作用分为轻度和重度脂肪肝/脂肪变性（分别为30和60天）和纤维化/肝硬化（90天）阶段。在定制的大鼠基因芯片上分析4900个克隆的表达水平，并通过半定量RT-PCR证实结果。在一个或多个时间点，438个克隆的差异表达超过1.625倍的差异（在log 2标度中等于0.7）。参与脂质代谢和核糖体生物合成的多个基因在慢性CCl 4给药后显示出不同的转录水平，这在以前的急性大鼠模型中也观察到。此外，通过倍数变化或微阵列的显著性分析，总共149个克隆被鉴定为纤维化/水肿特异性基因。总之，我们报告了慢性CCl 4给药后大鼠肝脏的微阵列分析结果，其完整的时间分布不仅涵盖了脂肪肝/脂肪变性，而且还涵盖了纤维化/肝硬化的后期点。这些数据将提供特定的基因表达谱的洞察力，涉及脂肪肝/脂肪变性和纤维化/肝硬化的多步骤过程后，慢性肝毒素暴露。(c)2005年爱思唯尔公司All rights reserved.
Global gene expression profile was analyzed by microarray analysis of rat liver RNA after chronic carbon tetrachloride (CCl4) administration. Rats received 0.5 MI CCl4/kg three times a week, and the liver samples were obtained after 0, 30, 60, and 90 days of injection. Histopathologic studies of liver tissues enabled the classification of the CCl4 effect into mild and severe fatty liver/steatosis (30 and 60 days, respectively) and fibrosis/cirrhosis (90 days) stages. The expression levels of 4900 clones on a custom rat gene microarray were analyzed and the results were confirmed by semi-quantitative RT-PCR. Four hundred thirty-eight clones were differentially expressed with more than a 1.625-fold difference (which equals 0.7 in log2 scale) at one or more time points. Multiple genes involved in lipid metabolism and ribosome biogenesis showed differential transcript levels upon chronic CCl4 administration, which was previously seen in acute rat model as well. In addition, a total of 149 clones were identified as fibrosis/cirrhosis-specific genes by either fold changes or Significance Analysis of Microarrays. In conclusion, we report microarray analysis results in rat liver upon chronic CCl4 administration with a full chronological profile that not only covered fatty liver/steatosis but also later points of fibrosis/cirrhosis. These data will provide the insight of specific gene expression profiles that is implicated in the multistep process of fatty liver/steatosis and fibrosis/cirrhosis after chronic hepatotoxin exposure. (c) 2005 Elsevier Inc. All rights reserved.