摘要: |
目的 比较3种饮食诱导的非酒精性脂肪性肝炎(NASH)小鼠模型的特征,从而为NASH的机制研究和药物研发提供参考。方法 分别用高脂饮食(HFD)喂养24周、Amylin饮食喂养24周、高脂-蛋氨酸胆碱缺乏饮食(HFMCD)喂养10周,诱导小鼠NASH表型,并用正常饮食(CD)小鼠作为对照,每组10只。喂养结束后分别检测其体质量、肝质量,血清转氨酶(肝脏损伤指标)、肝脏三酰甘油(肝脏脂质沉积指标)、肝脏羟脯氨酸(肝纤维化指标)水平,以及胰岛素敏感性。对小鼠肝组织切片进行苏木精-伊红(H-E)染色和天狼星红染色,以观察其组织学变化。结果 HFD组小鼠发生明显肥胖和胰岛素抵抗,血清转氨酶升高、肝脏三酰甘油沉积、肝脏羟脯氨酸沉积和肝脏组织炎症病变程度小。Amylin饮食组小鼠发生明显肥胖、胰岛素抵抗、血清转氨酶升高、肝脏三酰甘油沉积、肝脏羟脯氨酸沉积,以及严重的NASH肝脏组织病理学改变。HFMCD组小鼠诱导饮食后相对短时间内发生较严重的血清转氨酶上升、肝脏三酰甘油沉积、肝脏羟脯氨酸沉积和肝脏病理学改变,未发生胰岛素抵抗和肥胖。结论 3种饮食诱导的小鼠模型各有其特点,其中,Amylin饮食诱导的NASH模型更符合人NASH发生发展过程。 |
关键词: 非酒精性脂肪性肝炎 高脂饮食 Amylin饮食 高脂-蛋氨酸胆碱缺乏饮食 动物模型 |
DOI:10.12025/j.issn.1008-6358.2022.20220548 |
分类号:R575.1 |
基金项目:国家自然科学基金面上项目(81970740),上海市科委青年科技启明星计划(20QA1402000I). |
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Comparison of three diet-induced mouse models of nonalcoholic steatohepatitis |
MENG Qing-nan, ZHANG Xiao-fu, XIONG Xue-lian
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Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, 200032, China
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Abstract: |
Objective To compare different diet-induced nonalcoholic steatohepatitis (NASH) mouse models, so as to provide a reference for NASH related study. Methods Mice were randomly divided into four groups with 10 mice in each group. NASH models were established by feeding with high-fat diet (HFD) for 24 weeks, Amylin diet for 24 weeks, and high-fat methionine- and choline-deficient diet (HFMCD) for 10 weeks, respectively. 10 mice feeding by chow diet (CD) was used as control. After feeding, body weight, liver weight, serum transaminase, liver triglyceride (TG), and liver hydroxyproline levels were measured. Fasting blood glucose and insulin tolerance test (ITT) were used to assess insulin sensitivity. Hematoxylin-eosin (H-E) staining and Sirius red staining were used to indicate pathological changes of liver. Results The mice in HFD group had obesity and insulin resistance, mild serum transaminase, liver TG, liver hydroxyproline levels, and inflammatory changes in the liver. The mice in Amylin group occured obvious NASH accompanied with obesity and severe insulin resistance. The mice in HFMCD group had severe NASH phenotype changes in a relative short time, without obesity and insulin resistance. Conclusions All three diet-induced mouse models show different advantages and disadvantages. NASH models induced by Amylin diet recaptures the key NASH features observed in patients. |
Key words: nonalcoholic steatohepatitis high-fat diet Amylin diet high-fat methionine- and choline-deficient diet animal model |