摘要
背景:己酮可可碱(PTX)可减轻高脂饮食大鼠脂肪性肝炎和肝纤维化的程度,但其作用机制尚未明确。目的:探讨PTX对非酒精性脂肪性肝炎(NASH)大鼠肝脏基因表达谱的影响。方法:24只Sprague-Dawley大鼠在高脂饮食4周后随机分为模型组(n=12)和PTX干预组(n=12,PTX每天100mg/kg),并继续予高脂饮食;6只普通饮食饲养大鼠作为对照组。于实验第24周处死大鼠,应用含15650条基因的大鼠U230A芯片检测肝脏基因表达的改变。结果:与模型组相比,PTX干预组共出现370条差异表达基因,其中模型组较对照组上调而PTX干预后下调的基因57条,主要包括炎症/免疫反应相关基因、细胞信号转导相关基因、细胞外基质和细胞黏附分子基因、代谢酶和生物转化相关基因、离子通道/运输蛋白基因等;模型组较对照组下调而PTX干预后上调的基因25条,其功能涉及细胞信号转导、脂质代谢、生物转化等。结论:PTX可能通过影响NASH大鼠肝脏多种结构和功能基因的表达而有助于NASH和肝纤维化的防治。
Background： It has been proven that pentoxifylline （PTX） can improve steatohepatitis and fibrosis in rats fed with high fat diet. but its mechanism remains uncertain. Aims： To investigate the effects of PTX on hepatic gene expression profiling in a rat model of nonalcoholic steatohepatitis （NASH）. Methods： Thirty Sprague-Dawley rats were enrolled, among them, 24 fed with high fat diet for 4 weeks were randomly allocated into two groups, model group （n=12） and PTX- intervention group （n=12）. High fat diet was given continuously in both groups, and in the intervention group, PTX-contained drinking water （100 mg/kg per day） was supplied. Meanwhile, 6 rats fed with standard diet served as control group. All rats were sacrificed at the 24th week and the hepatic gene expressions were detected by oligonucleotide microarray analysis with Affymetrix GeneChip Rat U230A consisting of 15 650 genes. Results： The expression of 370 genes in the PTX-intervention group changed over twofold as compared with those in the model group, among which, 57 were up-regulated in the model group （r,s. control group）, but down-regulated after PTX-intervention （vs. model group）, including related genes of inflammatory/immune response, cellular signal transduction, extracellular matrix and cell adhesion molecules, metabolic enzyme and biotransformation, ion channels/transporters, etc; 25 were down-regulated in the model group, but up-regulated after PTX-intervention, the functions involved were cellular signal transduction, lipid metabolism, and biotransformation, etc. Conclusions： PTX can affect the expression of many structural and functional genes in the liver of NASH rats, and may be useful in the prevention and treatment of NASH and liver fibrosis.
出处
《胃肠病学》
2005年第5期263-268,共6页
Chinese Journal of Gastroenterology
基金
上海市青年科技启明星计划和跟踪计划(No.03QMH1409)资助
作者简介
范建高,Email：fanjg@citiz.net
