Fan Jian-gao, Fang Ji-wei, Lu Yuan-shan, Qian Yan, Cai Xiao-bo
Department of Digestive Diseases, Shanghai First People's Hospital, Jiaotong University, Shanghai 200080, China.
Zhonghua Gan Zang Bing Za Zhi. 2005 Aug;13(8):597-601.
To explore the changes of hepatic gene expression during the course of nonalcoholic fatty liver disease (NAFLD) development in rats.
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.
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 transport genes.
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.
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的变化。
通过给动物喂食高脂饮食24周建立NAFLD大鼠模型。使用覆盖15650个基因的大鼠U230A（Affymetrix基因芯片）在不同时间点分析模型大鼠和对照大鼠的肝脏组织。
与对照大鼠相比，模型组大鼠在4周和8周时表达差异的基因数量分别为426个和540个。其中上调的基因有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、细胞转录和分化基因。下调的基因有离子通道基因、激素受体基因和细胞骨架基因。在第12周，表达差异基因的数量为501个，其中352个为上调基因，包括白细胞介素和Toll样受体4等与炎症和凋亡相关的基因。在第16周，差异表达基因的数量为665个，上调430个，如与炎症和凋亡基因以及I型胶原和纤维化基因相关的基因，然而细胞再生基因下调。在第24周，该数量为663个，其中成纤维细胞生长因子、转化生长因子和胰岛素样生长因子基因上调。在所有差异表达基因中，上调基因有128个，包括10个脂肪生成基因、46个代谢基因、15个炎症基因、10个凋亡基因和16个纤维化基因；下调基因有52个，包括6个激素受体基因、5个细胞再生基因和11个电子传递基因。
高脂饮食喂养大鼠的肝脏基因表达变化与喂养持续时间有关，且与肝脏组织病理学相关。
