中国药物警戒 ›› 2026, Vol. 23 ›› Issue (1): 63-69.
DOI: 10.19803/j.1672-8629.20250463

• 基于海藻-甘草配伍研究专栏 • 上一篇    下一篇

海藻-甘草配伍对甲状腺肿大大鼠氧化应激和铁死亡水平的影响及机制探讨

张文康, 吴美晶, 于雪, 丁图南, 郭添添, 雷飞扬, 修琳琳*   

  1. 北京中医药大学中医学院,北京 100029
  • 收稿日期:2025-07-13 出版日期:2026-01-15 发布日期:2026-01-15
  • 通讯作者: *修琳琳,女,博士,副教授,中药药性理论与临床应用研究。E-mail: xiulinlin@bucm.edu.cn
  • 作者简介:张文康,女,在读本科,中药药性理论与临床应用研究。
  • 基金资助:
    国家自然科学基金资助项目(82104411、82274118); 北京中医药大学纵向科研发展基(2024-ZXFZJJ-JW-062)

Effects and Mechanisms of Haizao-Gancao Pair on Oxidative Stress and Thyroid Ferroptosis Levels in Rats with Goiter

ZHANG Wenkang, WU Meijing, YU Xue, DING Tunan, GUO Tiantian, LEI Feiyang, XIU Linlin*   

  1. School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China
  • Received:2025-07-13 Online:2026-01-15 Published:2026-01-15

摘要: 目的 探讨海藻甘草配伍对甲状腺肿大大鼠氧化应激和铁死亡的影响及其分子机制。方法 通过网络药理学平台挖掘海藻甘草配伍改善甲状腺肿的潜在作用机制;将78只Wistar大鼠随机分为对照组,模型组,优甲乐组,海藻甘草低、中、高剂量组(1.98、3.96、7.92 g·mL-1)。除对照组外,其余各组通过丙硫氧嘧啶(PTU)诱导建立甲状腺肿大鼠模型,并给予干预。28 d后,观察大鼠一般情况及甲状腺系数,检测氧化应激和铁死亡指标。结果 KEGG通路与GO分析多与氧化还原稳态调控、脂质代谢密切相关,且筛选出关键靶点PTGS2。动物实验显示模型组大鼠甲状腺系数升高,甲状腺滤泡结构紊乱等改变。海藻甘草各剂量组可明显改善甲状腺肿大鼠的一般状况和组织病理学特征,其中低剂量组效果最为显著;同时可上调氧化应激指数(OSI)(P<0.05)和活性氧(ROS)水平(P<0.001);普鲁士蓝染色和透射电镜显示:海藻甘草各剂量组的甲状腺组织出现特征性铁沉积和线粒体超微结构改变;海藻甘草低剂量组可激活Nrf2/HO-1信号通路(P<0.05,P<0.001),同时调控铁死亡关键标志物GPX4和PTGS2的表达(P<0.01,P<0.05)。结论 海藻甘草可通过Nrf2/HO-1/GPX4通路调控“氧化应激-铁死亡”信号轴改善甲状腺肿。

关键词: 海藻, 甘草, 氧化应激, 铁死亡, Nrf2/HO-1/GPX4, 超高效液相色谱-串联质谱联用技术, 大鼠

Abstract: Objective To investigate the therapeutic effects of Haizao and Gancao against oxidative stress and ferroptosis in goiter rats and the molecular mechanism. Methods Based on the network pharmacology platform, the potential mechanisms of action of Haizao and Gancao in ameliorating goiter were explored. Seventy-eight Wistar rats were randomly divided into a control group, model group, Euthyrox group, and low-, medium-, and high-dose groups of Haizao and Gancao (1.98、3.96、7.92 g·mL-1). Except the control group, all the groups were induced to establish a goiter rat model using propylthiouracil (PTU) and underwent corresponding interventions. After 28 days, the condition of the rats and thyroid coefficient were observed, and indicators of oxidative stress and ferroptosis were detected. Results KEGG pathway and GO analyses were closely correlated with the regulation of redox homeostasis and lipid metabolism, with PTGS2 identified as a key target. Animal experiments suggested that rats in the model group manifested hypometabolic symptoms and structural disorganization of thyroid follicles. Haizao and Gancao of varying doses significantly ameliorated the health status and histopathology of goitrous rats, with the efficacy most pronounced in the low-dose group. An oxidative stress imbalance was observed in goitrous model rats. The oxidative stress index (OSI) (P<0.05) and reactive oxygen species (ROS) levels (P<0.001) were upregulated in the low-dose Haizao and Gancao group. Prussian blue staining and transmission electron microscopy pointed to characteristic iron deposition and ultrastructural changes of mitochondria in thyroid tissues in each group. The Nrf2/HO-1 signaling pathway was activated while the expressions of key markers of ferroptosis-GPX4 and PTGS2- (P<0.05, P<0.001) were regulated in the low-dose Haizao and Gancao group (P<0.01, P<0.05). Conclusion Haizao and Gancao can ameliorate goiter by regulating the ‘oxidative stress-ferroptosis’ signaling axis through the Nrf2/HO-1/GPX4 pathway.

Key words: Haizao, Gancao, Oxidative Stress, Ferroptosis, Nrf2/HO-1/GPX4, UPLC-MS/MS, Rat

中图分类号: