实验动物与比较医学 ›› 2020, Vol. 40 ›› Issue (2): 123-127.DOI: 10.3969/j.issn.1674-5817.2020.02.006

• 论著 • 上一篇    下一篇

高脂饮食诱导的非酒精性脂肪肝病食蟹猴模型

高仕平, 李锋, 查思凡   

  1. 昆明科灵生物科技有限公司, 昆明 650550
  • 收稿日期:2019-02-12 出版日期:2020-04-25 发布日期:2020-12-18
  • 作者简介:高仕平(1992-), 女, 硕士, 兽医技术员, 从事非人灵长类动物相关工作。E-mail: 14787893597@163.com

High-fat Diet Induced Cynomolgus Monkey Model of Non-alcoholic Fatty Liver Disease

GAO Shiping, LI Feng, ZHA Sifan   

  1. Kunming Biomed International Ltd., Kunming 650550, China
  • Received:2019-02-12 Online:2020-04-25 Published:2020-12-18

摘要: 目的 建立高脂饲料诱导非酒精性脂肪肝病(NAFLD)食蟹猴动物模型,分析高脂饲料饲喂时间对动物NAFLD形成的影响,探索高脂饲料饲喂时间与血清中生化指标、肝脏脂肪化及纤维化形成的相关性。 方法 实验前对700只健康食蟹猴收集基础血液,然后用高脂饲料饲喂,分别在饲喂1年、2年、3年、4年、5年、6年和7年时,随机抽取部分实验猴,用盐酸氯胺酮麻醉并收集动物血液,检测血清中丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、甘油三酯(TG)、总胆固醇(TC)、高密度脂蛋白(HDL)、低密度脂蛋白(LDL)指标,并进行肝组织活检。结果 在饲喂高脂饲料2年时, 食蟹猴血清ALT、AST、TG、TC、LDL水平均显著升高,HDL水平显著下降(P<0.01)。高脂饲料饲喂2年及以上时间与ALT、AST、TG、TC、脂肪化、纤维化在0.01水平(双侧)上显著相关(r分别为0.127、0.121、0.246、0.128、0.306和0.220), 与HDL呈负相关(r=-0.298, P<0.05), 与LDL在0.05水平(双侧)上显著相关(r=0.081)。病理组织学观察显示,随时间推移肝脏发生严重的脂肪变性和气球样变性、脂肪肝,进而发生肝炎、纤维化。结论 高脂饮食可导致食蟹猴血脂及肝酶活性指标明显升高,肝脏脂质聚集,炎性浸润明显,表明高脂饮食能够成功诱导NAFLD食蟹猴模型并促进NAFLD的进展。

关键词: 食蟹猴, 非酒精性脂肪肝病, 高脂饲料, 动物模型

Abstract: Objective To establish non-alcoholic fatty liver disease (NAFLD) animal model induced by high-fat diet, and to analysis the effect of high-fat feeding time for animal NAFLD formation, exploring the correlation between feeding time of high-fat diet and serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglycerides (TG), total cholesterol (TC), high-density lipoprotein (HDL), low density lipoprotein (LDL), fatty liver, and fibrosis formation. Methods Before the experiment, basic blood samples were collected from 700 healthy cynomolgus monkeys, then fed with high-fat diet, some of the monkeys were sampled at 1, 2, 3, 4, 5, 6 and 7 years respectively after being fed with high-fat diet and anaesthetized with ketamine hydrochloride, and the blood were collected for detection of ALT, AST, TG, TC, HDL and LDL indicators, and liver tissue biopsy was performed. Results After 2 years of high-fat feed, the serum ALT, AST, TG, TC and LDL levels of cynomolgus monkeys were significantly increased (P<0.01), and HDL level was significantly decreased (P<0.01). The feeding time of high-fat feed was significantly correlated with ALT, AST, TG, TC, liver adipose and fibrosis at the level of 0.01 (bilateral) (r=0.127, 0.121, 0.246, 0.128, 0.306, 0.220), but negatively correlated with HDL (r=-0.298, P<0.05), and significantly correlated with LDL at the level of 0.05 (bilateral) (r=0.081). Histopathology showed that serious fatty degeneration and balloon-like degeneration occurred in the liver over time, fatty liver followed by hepatitis and fibrosis. Conclusion The high-fat diet can significantly increase blood lipid and liver enzyme activity indexes in cynomolgus monkeys, the liver lipid aggregation and inflammatory infiltration are obvious, indicating that high-fat diet can successfully induce NAFLD model and promote the development of NAFLD.

Key words: Cynomolgus monkeys, No-alcoholic fatty liver disease, High-fat diet, Animal models

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