【摘要】 目的 构建高脂饮食诱导的非酒精性脂肪肝（NAFLD）大鼠模型，分析该模型大鼠肝脏的差异代谢物，探究NAFLD大鼠模型代谢特征。方法 SPF级SD大鼠12只，雌雄各半，体重90～110 g，根据体重随机分为模型组和正常组。采用高脂饮食诱导法建立NAFLD大鼠模型，正常组给予普通维持饲料，模型组给予高脂饲料（配方为：78.8%基础饲料+10%猪油+10%蛋黄粉+1%胆固醇+0.2%胆酸钠），造模第8周取材，生化法检测谷丙转氨酶（ALT）、谷草转氨酶（AST）、总胆固醇（TC）、三酰甘油（TG）、低密度脂蛋白胆固醇（LDL-C）、高密度脂蛋白胆固醇（HDL-C）等指标；HE染色观察肝脏病理变化；运用高效液相色谱-质谱联用技术分析大鼠肝脏非靶向代谢物变化。结果 与正常组比较，模型组大鼠肝脏指数和肥胖指数显著升高（P <0.05或0.01），血清TC、TG、LDL-C、ALT显著升高（P <0.05或0.01），肝脏TC、TG、LDL-C显著升高（P <0.01）,HDL-C显著降低（P <0.05）。HE染色结果显示，模型组大鼠肝组织脂肪变性、气球样变和炎细胞浸润，NAS评分显著升高（P <0.01）。肝脏代谢组学共筛选出253个差异代谢物，获取了视黄醇代谢、不饱和脂肪酸的生物合成等代谢通路。结论 高脂饮食8周可成功建立NAFLD大鼠模型，其代谢组学变化涉及视黄醇代谢、不饱和脂肪酸的生物合成等多个代谢途径。更多还原

【Abstract】 Objective To establish a high-fat diet induced rat model of non-alcoholic fatty liver disease(NAFLD), to analyze the differential metabolites in the liver of the model rat, and to explore the metabolic characteristics of the NAFLD rat model. Methods Totally 12 SPF SD rats, 6 males and 6 females, with the body weight of 90 ～ 110 g, were randomly divided into a model group and a normal group according to body weight. High-fat diet induction was used to establish a NAFLD rat model. The normal group was given regular maintenance feed, while the model group was given high-fat feed(high fat feed formula: 78.8% basic feed + 10% lard + 10% egg yolk powder +1% cholesterol + 0.2% sodium cholate). At the 8th week of modeling, samples were taken, and alanine transaminase(ALT), aspartate transaminase(AST), total cholesterol(TC), triglyceride(TG),low density lipoprotein cholesterol(LDL-C), high-density lipoprotein cholesterol(HDL-C) and other indicators were biochemically detected. HE staining was used to detect the liver pathological changes, and analyze non-targeted changes in rat liver metabolites with high-performance liquid chromatography mass spectrometry. Results Compared with the normal group, the liver index and obesity index of the model group were increased(P < 0.05 or 0.01), while TC, TG, LDL-C, and ALT in the serum of the model group were increased(P < 0.05 or 0.01). TC, TG, and LDL-C in the liver were increased(P < 0.01), while HDL-C was reduced(P < 0.05). HE staining showed that the NAS score of steatosis, ballooning and inflammatory cell infiltration in the liver tissue of rats in the model group increased significantly(P < 0.01). Totally 253 differential metabolites were screened out by liver metabolomics, and metabolic pathways such as retinol metabolism and unsaturated fat acid biosynthesis were obtained. Conclusion An NAFLD rat model is successfully established after 8weeks of high-fat diet, whose metabonomic changes included retinol metabolism, unsaturated fat acid biosynthesis and other metabolic pathways.更多还原