摘要
目的探讨大鼠非酒精性脂肪性肝病(NAFLD)发生过程中肝脏基因表达谱的改变。方法通过持续24周高脂饮食诱导大鼠NAFLD模型,应用U230A芯片检测不同造模时期肝脏基因表达,并设普通饮食饲养大鼠作对照。结果与对照大鼠相比,造模4周和8周时差异表达基因数分别为426条和540条, 上调基因主要为细胞内磷酸化酶基因、代谢酶基因、脂肪酸结合蛋白基因、细胞色素P450基因以及细胞转录和分化基因等,下调基因主要为离子通道基因、激素受体基因、细胞黏附基因以及细胞骨架基因等;12 周时差异表达基因有501条,其中表达上调352条,除上述基因外,还包括白细胞介素、Toll样受体4等炎症和凋亡相关基因;16周时差异表达的基因有665条,其中上调基因430条,炎症和凋亡相关基因表达进一步增加,且Ⅰ型胶原等纤维化相关基因出现表达上调,而细胞再生相关基因表达下调;24周时差异表达的基因有663条,其中上调基因512条,除上述基因表达差异外,主要包括成纤维细胞生长因子、转化生长因子和胰岛素样生长因子等纤维化相关基因。在所有表达差异的基因中,随着时间进展表达持续上调的基因共128条,其中成脂相关基因10条,代谢酶基因46条,炎症相关基因15条、凋亡相关基因10条,纤维化相关基因16条;持续下调的基因有52条,包括激素受体相关基因6条,细胞再生相关基因5条,电子转运基因11条等。结论高脂饮食大鼠肝脏基因谱呈动态改变,并与NAFLD的组织学进展一致。
Objective To explore the changes of hepatic gene expression during the course of nonalcoholic fatty liver disease （NAFLD） development in rats. Methods A rat model of NAFLD was developed by feeding the animals a high-fat diet for 24 weeks. Liver tissues of the model rats and the control rats were analyzed at different time points using rat U230A （Affymetrix GeneChip）, which covers 15650 genes. Results Compared with the control rats, the number of genes expressed differently in the model group rats at 4 and 8 weeks was 426 and 540. The up-regulated genes among them were intracellular phosphorylase genes, metabolic enzyme genes, fatty acid binding protein genes, cytochrome P450 genes, cellular transcription and differentiation genes. The down-regulated genes were ionic channel genes, hormone receptor genes, and cytoskeleton genes. At the 12th week, the number of the genes expressed differently was 501, in which 352 were up-regulated genes, including genes related to inflammation and apoptosis such as interleukin and Toll-like receptor 4. At the 16th week, the number of the differently expressed genes was 665, with 430 up-regulated, such as those related to the inflammation and apoptosis genes and collagen Ⅰ and fibrosis genes, however cell regeneration genes were down-regulated. At the 24th week the number was 663, of which fibroblast growth factor, transforming growth factor and insulin-like growth factor genes were up-regulated. Of all the differently expressed genes, the number of up-regulated genes was 128, including 10 lipogenic genes, 46 metabolic genes, 15 inflammation genes, 10 apoptosis genes, and 16 fibrosis genes; and the down-regulated genes were 52, including 6 hormone receptor genes, 5 cell regeneration genes and 11 electron tranport genes. Conclusion The changes of the hepatic gene expression of rats fed a fat-rich diet are related to the duration of the feeding, and are correlated with their histopathology in the livers.
出处
《中华肝脏病杂志》
CAS
CSCD
北大核心
2005年第8期597-601,共5页
Chinese Journal of Hepatology
基金
上海市青年科技启明星跟踪计划(03QMH1409)
