Kojima K, Hosokawa M, Kobayashi K, Tainaka H, Chiba K
Laboratory of Pharmacology and Toxicology, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba-shi, Japan.
Res Commun Mol Pathol Pharmacol. 2004;115-116:63-75.
Cholestasis is one of the major liver diseases and results in progressive liver fibrosis and cirrhosis. In this study, the transcriptional response of the liver to common bile duct ligation in rats was examined by cDNA microarray analysis, and 134 genes for which expression was altered during long-term cholestasis were identified. Clustering analysis of these genes for multiple time-point data yielded 7 different patterns in which a large portion of the genes was classified into 3 clusters. Two clusters consisted of up-regulated genes, including genes that may be related to disruption of lipid metabolism and liver fibrosis observed in the early stage of cholestasis, and the other cluster consisted of down-regulated genes, including a gene that has been thought to be involved in the mechanism of cell protection against accumulation of bile acids. Since the expression patterns of these genes appear to reflect molecular features of cholestasis. Characterization of the genes identified in this study may shed further light on the physiological and pathological characteristics of long-term cholestasis.
胆汁淤积是主要的肝脏疾病之一，会导致进行性肝纤维化和肝硬化。在本研究中，通过cDNA微阵列分析检测了大鼠肝脏对胆总管结扎的转录反应，鉴定出134个在长期胆汁淤积期间表达发生改变的基因。对这些基因的多个时间点数据进行聚类分析，得出7种不同模式，其中大部分基因被分为3个簇。两个簇由上调基因组成，包括可能与胆汁淤积早期观察到的脂质代谢紊乱和肝纤维化相关的基因，另一个簇由下调基因组成，包括一个被认为参与细胞保护机制以防止胆汁酸积累的基因。由于这些基因的表达模式似乎反映了胆汁淤积的分子特征。本研究中鉴定出的基因特征可能会进一步揭示长期胆汁淤积的生理和病理特征。
