天然产物研究与开发 ›› 2024, Vol. 36 ›› Issue (增刊2): 26-36.

• 研究论文 • 上一篇    下一篇

高腺嘌呤饮食致慢性间质性肾损伤小鼠模型的建立与评价

李   丽1,2,3,魏立新1,2,张   明1,2*,李天才1,2*   

  1. 1中国科学院西北高原生物研究所 青海省藏药药理学与安全性评价研究重点实验室;2中国科学院藏药重点实验室,西宁 810008;3中国科学院大学,北京 100049
  • 出版日期:2024-12-09 发布日期:2024-12-09
  • 基金资助:
    青海省重大科技专项(2021-SF-A4);内蒙古自治区科技成果转化专项(2021CG0025)

Establishment and evaluation of a mouse model of chronic interstitial kidney injury induced by high adenine diet

LI Li1,2,3,WEI Li-xin1,2,ZHANG Ming1,2*,LI Tian-cai1,2*   

  1. 1Qinghai Key Laboratory for Pharmacology and Safety Evaluation of Tibetan Medicine,Northwest Institute of Plateau Biology,Chinese Academy of Sciences;2Key Laboratory for Research of Tibetan Medicine,Chinese Academy of Sciences,Xining 810008,China;3University of Chinese Academic of Sciences,Beijing 100049,China
  • Online:2024-12-09 Published:2024-12-09

摘要:

本研究旨在建立一种高腺嘌呤饮食诱导的慢性间质性肾损伤小鼠模型。使用24周龄C57BL/6J雄性小鼠,通过灌胃和含腺嘌呤饲料两种方式给予实验小鼠腺嘌呤,实验周期为8周,包含诱导期、转化发展期和干预期。模型评价指标包括一般生理学指标、肾功能参数、组织病理学变化以及纤维化相关因子等。在一般生理学指标方面,模型组实验小鼠体重、体温、进食量和活动性下降,饮水量、尿量上升;在肾功能指标方面,模型组实验小鼠血清肌酐、尿素氮、尿酸含量上升,尿液肌酐、尿蛋白/肌酐比上升,渗透压下降;在组织病理学方面,模型组实验小鼠出现肾小管扩张以及广泛轻度纤维化等病理变化,Masson染色阳性面积比上升;在纤维化相关因子方面,模型组实验小鼠肾脏中转化生长因子-β1(transforming growth factor-β1,TGF-β1)表达上升,硫化氢含量降低。本研究建立的慢性间质性肾损伤小鼠模型,符合慢性间质性肾损伤的疾病特征,适用于慢性间质性肾损伤的病理机制研究以及治疗药物评价。

关键词: 腺嘌呤, 慢性肾病, 间质性肾损伤, 别嘌呤醇, 硫化氢

Abstract:

The aim of this study was to establish a mouse model of chronic interstitial kidney injury induced by a high adenine diet.Twenty-four week-old C57BL/6J male mice were given adenine by gavage and adenine-containing diet.The experiment period was eight weeks,including induction period,transformation and development period and intervention period.The evaluation indexes of the model included general physiological indexes,renal function parameters,histopathological changes and fibrosis-related factors.In terms of general physiological indexes,the body weight,body temperature,food intake and activity of the model group decreased,while the water and urine volume increased.In terms of renal function indexes,the contents of serum creatinine,urea nitrogen and uric acid increased,urine creatinine and urine protein/creatinine ratio increased,and osmotic pressure decreased in the model group.In terms of histopathology,pathological changes such as renal tubule dilation and extensive mild fibrosis were observed in the model group,and the MASSON-positive area ratio increased.In terms of fibrosis-related factors,the expression of transforming growth factor-β1(TGF-β1) in the kidney of mice in the model group increased,and the content of hydrogen sulfide decreased.The mouse model of chronic interstitial kidney injury established in this study is consistent with the disease characteristics of chronic interstitial kidney injury,and is suitable for the study of pathological mechanism and therapeutic drug evaluation of chronic interstitial kidney injury.

Key words: adenine, chronic kidney disease, interstitial kidney injury, allopurinol, hydrogen sulfide

中图分类号:  R965.1