【摘要】 目的:建立并研究高脂饲料(HFD)联合不同浓度葡聚糖硫酸钠(DSS)饮水导致小鼠非酒精性脂肪肝炎(NASH)的动物模型,确定最适DSS浓度。方法:雄性昆明小鼠80只,随机分为8组,即正常对照组、HFD组、2%DSS组、2%DSS+HFD组、2.5%DSS组、2.5%DSS+HFD组、3%DSS组、3%DSS+HFD组。高脂组均给予高脂饲料,饲养1周后给予5 d相应浓度的DSS溶液,再换正常饮水。2周后处死,HE染色观察结肠和肝脏组织形态,油红O染色观察肝脏脂质沉积情况,RT-PCR检测肝脏chREBF、IL-6的表达情况。结果:组织病理结果显示,3种浓度DSS联合高脂组肝脏均有脂质沉积,并且与DSS浓度呈正相关;3种浓度DSS联合高脂组的结肠损伤与肝损伤结果一致。3种浓度DSS联合高脂组的脂代谢相关基因表达增加,与肝脏组织学结果一致,同时炎症因子表达升高,其中2.5%DSS高脂联合组IL-6表达显著上调(P<0.001)。结论:给予DSS可加速高脂饮食诱导小鼠NASH模型的建立,且在本研究中确立2.5%DSS为最适浓度。更多还原

【Abstract】 Objective:To construct and research on nonalcoholic steatohepatitis(NASH) mouse model induced by high fat diet(HFD) as well as dextransulfatesodium(DSS) and to determine the optimal concentration of DSS.Methods:80 male Kunming mice were randomly divided into 8 groups:normal control group,HFD group,2%DSS group,2%DSS+HFD group,2.5%DSS group,2.5%DSS+HFD group,3%DSS group,3%DSS+HFD group.The high-fat group was given high-fat diet,and after a week of feeding,corresponding concentration of DSS aqueous solution was given for 5 days,and then changed to normal drinking water.After 2 weeks,morphology of colon and liver were observed by HE staining.The lipid deposition was observed by oil red O staining.The expressions of chREBF and IL-6 in liver were detected by RT-PCR.Results:Histopathological results showed that there were lipid deposition in liver of the three concentrations of DSS combined with high-fat group,and it was positively correlated with DSS concentration.Colonic injury was consistent with liver injury in the three concentrations of DSS combined with high-fat group.Expression of lipid metabolism-related genes in the three concentrations of DSS combined with high-fat group were increased,which consistent with liver histology and increased expression of inflammatory factors.The expression of IL-6 in the 2.5% DSS high-fat combination group was significantly up-regulated(P<0.001).Conclusion:DSS administration can accelerate establishment of NASH model induced by high-fat diet,and determined 2.5% DSS as the optimal concentration in this study.更多还原