中国药物警戒 ›› 2024, Vol. 21 ›› Issue (4): 415-421.
DOI: 10.19803/j.1672-8629.20240081

• 基础与临床研究 • 上一篇    下一篇

多肽BR0336在小鼠2型糖尿病合并非酒精性脂肪性肝炎模型上的初步药效学研究

黄曙光1,2, 张学农1,*   

  1. 1苏州大学药学院,江苏 苏州,215000;
    2博瑞生物医药（苏州）股份有限公司,江苏 苏州,215000
  • 收稿日期:2024-02-04 出版日期:2024-04-15 发布日期:2024-04-18
  • 通讯作者: *张学农,男,教授·博导,药物新技术与新剂型研究。E-mail: zhangxuenong@163.com
  • 作者简介:黄曙光,男,在读硕士,药物制剂研究。
  • 基金资助:
    江苏省自然科学基金资助项目（BK20130645）

Pharmacodynamics of peptide drug BR0336 in a mouse model of T2DM combined with NASH

HUANG Shuguang1,2, ZHANG Xuenong1,*   

  1. 1College of Pharmaceutical Sciences, Soochow University Suzhou Jiangsu 215000, China;
    2BrightGene Bio-medical Technology Co., Ltd, Suzhou Jiangsu 215000, China
  • Received:2024-02-04 Online:2024-04-15 Published:2024-04-18

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摘要： 目的 研究多肽BR0336注射液在STZ-HFD诱导的雄性C57BL/6小鼠2型糖尿病（T2DM）合并非酒精性脂肪性肝炎（NASH）模型上的药效学。方法 新生雄性小鼠通过链脲佐菌素诱导建立T2DM模型,从1个月龄起开始给予高脂饲料喂养,根据空腹血糖和体重随机分为模型组、替西帕肽（TZP）的0.15 mg·kg-1阳性对照组和BR0336的低（0.05 mg·kg-1）、中（0.15 mg·kg-1）、高（0.5 mg·kg-1）剂量组,通过与正常对照组比较,考察小鼠体重、摄食量、空腹血糖、血清胰岛素、糖化血红蛋白、肝功能和血脂情况,并进行肝脏组织病理学NAS和纤维化分析。结果 BR0336各剂量组能显著降低模型小鼠的体重、摄食量、空腹血糖、胰岛素和HbA1c%,减低肝脏NAS评分和纤维化率,并对模型动物的肝功能和血脂异常具有良好保护作用。与阳性对照组相比,等剂量BR0336在动物的摄食量、胰岛素、肝功能和血脂生化方面表现更优,能更有效延缓NASH和纤维化进程。结论 BR0336对STZ-HFD诱导的T2DM合并NASH模型小鼠在高血糖和脂质代谢紊乱方面具有一定治疗作用。

关键词: BR0336, 2型糖尿病, 非酒精性脂肪性肝炎模型, 小鼠, GLP-1/GIP双重受体激动剂, 药效学

Abstract: Objective To investigate the pharmacological efficacy of the peptide-based drug BR0336 injection in a male C57BL/6 mouse model of T2DM combined with NASH induced by STZ-HFD. Methods Neonatal male mice were induced with streptozotocin to establish a T2DM model and fed a high-fat diet from one month of age. They were randomly assigned to the model group, TZP-0.15 mg∙kg-1 control group, and BR0336-0.05 mg∙kg-1, 0.15 mg∙kg-1, 0.5 mg∙kg-1 groups based on fasting blood glucose levels and body weight. Such parameters as body weight, food intake, fasting blood glucose, serum insulin, HbA1C%, liver function and blood lipid profiles of mice were recorded. Additionally, histopathological NAS and fibrosis analysis of liver tissues was conducted. Results BR0336 at various doses could significantly reduce body weight, food intake, fasting blood glucose, insulin levels and HbA1c% of model mice, and decrease liver NAS scores and fibrosis rates. Furthermore, BR0336 could protect liver function and improve dyslipidemia in model mice. Compared with the positive control group, an equivalent dose of BR0336 exhibited superior effects in terms of food intake, insulin levels, liver function and blood lipid profiles, and significantly delayed the progression of NASH and fibrosis. Conclusion BR0336 has a significant therapeutic effect against hyperglycemia and lipid metabolism disorders in model mice of STZ-HFD-induced T2DM combined NASH.

Key words: BR0336, T2DM, NASH model, mice, GLP-1/GIP double receptor agonist, pharmacodynamics

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