非酒精性脂肪性肝病大鼠肝脏基因表达谱分析

ldentificalion of gene expression patterns in rat model of nonalcoholic fatty liver disease

目的比较非酒精性脂肪性肝病（NAFLD）相关基因的差异表达，方法SD大鼠12只，根据体重分层，随机分为对照组和模型组，分别给予基础饲料和高脂饲料喂养4周，观察各组肝脏病理学改变，并用基因芯片技术比较两组大鼠肝脏基因表达睹差异、结果模型组大鼠高脂饲料喂养4周后，出现弥漫性肝细胞脂肪变性，伴小灶性炎性细胞浸润。根据基因芯片上目标基因荧光强度进行定量分析，取均值的比值后筛选出2倍以上的差异基因51条（P〈0.01），具中上调基因20条，包括固醇调节元件结合因子1、硬脂酰辅酶A去饱和酶1和Bcl-2修饰因子等；下凋基因31条，如过氧化酶体烯酰辅酶A水合酶1、热休克蛋白1A和ATP酶抑制因子等。上调基因主要参与脂质合成和细胞凋亡，而下调基因主要参与脂肪酸氧化、蛋白质修饰和能量代谢等过程。结论NAFLD的发病涉及多种基因表达改变。

Objective To compare： and analyze gene expression pattterns in rat model of nonalcoholic fatty liver disease （NAFLD）. Methods Twelve male Sprague-Dawley rats wcre randomly given either general diet （control group） or a high-fat diet （model group） for 4 weeks. The histopathologie changes of the liver were observed and gene expression patterns were analyzed and compared by cDNA microarray. Results Hepatocellular stealosis and inflammatory infiltration were observed in model group after high-fat diet for 4 weeks. Fifty-one differential genes were found in model group. 20 of which were up regulated （sterol regulatory element binding factor 1. stearoyl-coenzyme A desaturase 1 and Bcl 2 modifying factor） and 31 were down-regulated （peroxisomal enoyl coenzyme A hydratase 1. heat shock 70 protein 1A attd ATPase inhibitory factor 1）. The up-regulating genes were involved in hpogenesis and cell apoptosis, while down-regulated genes were involved in fatty acid oxidation, protein modification and energy metabolism. Conclusions The differential expression of genes may involve in the pathogenesis of NAFLD.