中国药物警戒 ›› 2023, Vol. 20 ›› Issue (3): 273-276.
DOI: 10.19803/j.1672-8629.20220559

• 基础与临床研究 • 上一篇    下一篇

2型糖尿病合并非酒精性脂肪性肝病KKAy动物模型的探索与评价

王姗1, 黄举凯1, 吴宏辉1, 温雅璐1, 张力2, 王建华3, 杨晓晖1,*   

  1. 1北京中医药大学东直门医院肾病内分泌二区,北京 100700;
    2北京中医药大学东方医院科研处,北京 100078;
    3首都儿科研究所,北京 100020
  • 收稿日期:2022-09-22 出版日期:2023-03-15 发布日期:2023-03-17
  • 通讯作者: * 杨晓晖,男,主任医师·博导,内分泌系统疾病中医临床与基础研究。E-mail:yxh0616@126.com
  • 作者简介:王姗,女,博士,内分泌系统疾病中医临床与基础研究。
  • 基金资助:
    国家自然科学基金资助项目(81974541)

Evaluation of a KKAy animal model of type 2 diabetes mellitus combined with nonalcoholic fatty liver disease

WANG Shan1, HUANG Jukai1, WU Honghui1, WEN Yalu1, ZHANG Li2, WANG Jianhua3, YANG Xiaohui1,*   

  1. 1Department of Nephrology and Endocrinology, Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, Beijing 100700, China;
    2Scientific Research Department, Dongfang Hospital Affiliated to Beijing University of Chinese Medicine, Beijing 100078, China;
    3Capital Institute of Pediatrics, Beijing 100020, China
  • Received:2022-09-22 Online:2023-03-15 Published:2023-03-17

摘要: 目的 探索2型糖尿病合并非酒精性脂肪性肝病KKAy动物模型的年龄节点和稳定性。方法 12周龄C57BL/6J小鼠18只作为对照组,普通饲料喂养;KKAy小鼠18只作为模型组,高脂饲料喂养。对照组和模型组分别于14、18、22周龄各随机处死6只小鼠,检测血糖、体重、肝功、血脂等指标,观察病理学形态改变情况。结果 与对照组相比,自14周龄起,模型组小鼠体重、肝重、肝重指数、血糖水平显著增加(P< 0. 05),模型组血糖水平符合糖尿病改变。血清学结果显示,与对照组相比,模型组小鼠的谷丙转氨酶(ALT)、谷草转氨酶(AST)、胆固醇(CHOL)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)水平显著升高(P<0.05),2组小鼠甘油三酯(TG)水平未形成显著性差异(P>0.05)。病理染色显示,14周龄模型组小鼠存在肝细胞脂肪变性,22周龄出现炎性细胞浸润。结论 14周龄KKAy小鼠经高脂饮食诱导可作为研究2型糖尿病合并非酒精性脂肪性肝病稳定的动物模型。

关键词: 2型糖尿病, 非酒精性脂肪性肝病, KKAy小鼠, 动物模型

Abstract: Objective To explore the age of onset and stability of a KKAY animal model of type 2 diabetes mellitus combined with nonalcoholic fatty liver disease. Methods Eighteen twelve-week-old C57BL/6J mice were assigned to the control group that was fed with normal diets while another 18 twelve-week-old KKAy mice served as the model group that was fed with high-fat diets. Six mice in control and model group were randomly killed at the 14,18,22 weeks of age, respectively. Blood glucose, weight, serum liver function and lipid levels were monitored and the pathological changes of hepatic tissues were observed. Results Compared with the control group, the body mass, liver mass, liver index and blood glucose level of the model group increased significantly (P< 0.05) from the 14th week. The results of serology showed that the ALT, AST, CHOL, HDL-C and LDL-C levels were significantly increased compared with the control group (P< 0.05), but no significant difference was found in TG levels between the two groups (P> 0.05). Pathological staining showed both steatosis of hepatocytes in the 14th week and inflammatory cell infiltration in the 22nd week. Conclusion The 14-week-old KKAy mice treated with high fat diets can serve as a stable mouse model of type 2 diabetes mellitus combined with nonalcoholic fatty liver disease.

Key words: type 2 diabetes mellitus, nonalcoholic fatty liver disease, KKAy mice, animal model

中图分类号: