金仓鼠非酒精性脂肪肝模型的建立及代谢组学分析

Cuiyun Zhao, Lin Jiang, Wenyan Li, Guang Wu, Jie Chen, Li-Hua Dong, Min Li, Wei Jiang, Ji-xiao Zhu, Yanxiang Gao, Qin-Ge Ma, G. Zhong, R. Wei
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摘要

目的建立高脂、高果糖、高胆固醇饲粮(HFFCD)致金仓鼠非酒精性脂肪性肝病(NAFLD)模型,探讨NAFLD模型特点及肝组织代谢物变化。金仓鼠分别饲喂HFFCD或对照饲料6周。评估体重、腹部脂肪指数和肝脏指数,检查血清参数、肝脏组织学和肝脏代谢物。结果显示,模型组大鼠体重、腹部脂肪、肝脏指数均显著升高,血清总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白-胆固醇(LDL-C)水平均显著升高,高密度脂蛋白-胆固醇(HDL-C)水平均显著降低。此外,肝组织内脂质沉积形成大小不等的脂肪空泡。肝脏代谢组学分析显示,在NAFLD模型中,鞘脂、甘油磷脂和精氨酸生物合成的代谢途径被扰乱。建模方法简单、时间短、均匀。可以模拟常见饮食因素引起的早期脂肪肝,为研究NAFLD的初始发病机制和治疗药物提供了理想的模型。
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Establishment and metabonomics analysis of nonalcoholic fatty liver disease model in golden hamster
Abstract The aim is to establish a model of nonalcoholic fatty liver disease (NAFLD) caused by feeding with high-fat, high-fructose, and high-cholesterol diet (HFFCD) in golden hamsters, and to investigate the characteristics of the NAFLD model and metabolite changes of liver tissue. Golden hamsters were fed HFFCD or control diets for six weeks. Body weight, abdominal fat index, and liver index was assessed, serum parameters, hepatic histology, and liver metabolites were examined. The results showed that body weight, abdominal fat, and liver index of hamsters were significantly increased in the model group, the level of serum total cholesterol (TC), triglyceride (TG), and low density lipoprotein-cholesterol (LDL-C) were significantly increased in model group as well, and high density lipoprotein-cholesterol (HDL-C) was significantly decreased. In addition, lipid deposition in liver tissue formed fat vacuoles of different sizes. Metabonomics analysis of the liver showed that the metabolic pathways of sphingolipid, glycerophospholipids, and arginine biosynthesis were disordered in the NAFLD model. The modeling method is simple, short time, and uniform. It can simulate the early fatty liver caused by common dietary factors, and provides an ideal model for the study of the initial pathogenesis and therapeutic drugs for NAFLD.
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