Page 130 - 《中国药科大学学报》2026年第2期

学报
256 Journal of China Pharmaceutical University 2026, 57(2): 256 − 265

齐多夫定通过促进脂肪酸氧化改善高脂饮食

诱导的大鼠代谢紊乱

张 靖 ，金子爱 ，王紫悦 ，林君谦 ，王 涛 1,2**
1,2*
1,2
1,2
1,2
1
（ 中国药科大学多靶标天然药物全国重点实验室新药筛选中心, 南京 210009；
2 江苏省药效研究与评价服务中心, 南京 210009）
摘 要 探讨齐多夫定（AZT）对高脂饮食（HFD）诱导大鼠代谢紊乱的改善作用及其潜在机制。通过建立 HFD 大鼠模
型，设置正常对照组、模型组及 AZT 低剂量（25 mg/kg）和高剂量（50 mg/kg）干预组，评价 AZT 对代谢表型、肝脏脂质沉
积、氧化应激、线粒体功能以及过氧化物酶体增殖物激活受体（PPAR）信号通路的影响。结果显示，与模型组相比，AZT 显
著抑制体重增长，降低腹股沟白色脂肪组织及附睾白色脂肪组织的重量和细胞体积，增强代谢灵活性，并改善葡萄糖耐量且
不引起血乳酸升高。高剂量 AZT 能进一步降低肝脏甘油三酯水平，减轻脂肪变性，并通过提高超氧化物歧化酶（SOD）活
性、降低丙二醛（MDA）水平以缓解肝脏氧化应激。蛋白免疫印迹实验结果显示，AZT 可上调肝脏 PPARα 及肉碱棕榈酰转
移酶 1α（CPT1α）蛋白表达，下调 PPARγ 表达。综上，AZT 能有效改善 HFD 诱导的代谢紊乱且未引起线粒体毒性，其作用
可能与促进脂肪酸氧化、减轻氧化应激、调控 PPAR 通路和嘧啶代谢有关。
关键词 齐多夫定；高脂饮食；代谢紊乱；脂肪酸氧化；氧化应激；线粒体功能；PPAR 信号通路
中图分类号 R965 文献标志码 A 文章编号 1000−5048(2026)02−0256−10
doi：10.11665/j.issn.1000−5048.2025102401

引用本文 张靖，金子爱，王紫悦，等. 齐多夫定通过促进脂肪酸氧化改善高脂饮食诱导的大鼠代谢紊乱 [J]. 中国药科大学学报，2026，
57（2）：256-265.

Cite this article as: ZHANG Jing, JIN Ziai, WANG Ziyue, et al. Zidovudine ameliorates metabolic disorders in HFD-fed rats by enhancing
fatty acid oxidation[J]. J China Pharm Univ, 2026, 57(2): 256-265.

Zidovudine ameliorates metabolic disorders in HFD-fed rats by enhancing

fatty acid oxidation
1,2
1,2*
1,2
1,2
ZHANG Jing , JIN Ziai , WANG Ziyue , LIN Junqian , WANG Tao 1,2**
1
Center for New Drug Screening, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009;
2
Jiangsu Center for Pharmacodynamics Research and Evaluation, Nanjing 210009, China
Abstract This study aimed to investigate the effects of zidovudine (AZT) on high-fat diet (HFD)-induced
metabolic disturbances in rats and its underlying mechanisms. The HFD rat model was established, and the
animals were divided into the control group, the model group, and the AZT-treated group at low (25 mg/kg) and
high (50 mg/kg) doses. Metabolic phenotype, hepatic lipid deposition, oxidative stress, mitochondrial function,
and peroxisome proliferator-activated receptor (PPAR) signaling were evaluated. AZT treatment significantly
mitigated HFD-induced body weight gain and reduced both the mass and adipocyte size of inguinal and
epididymal white adipose tissues; it also enhanced metabolic flexibility and improved glucose tolerance without
elevating blood lactate levels. High-dose AZT further lowered hepatic triglyceride accumulation, ameliorated
steatosis, and additionally, attenuated hepatic oxidative stress by increasing superoxide dismutase (SOD) activity
and decreasing malondialdehyde (MDA) levels. Western blot analysis revealed that AZT upregulated hepatic
PPARα and carnitine palmitoyltransferase 1α (CPT1α), while downregulating PPARγ expression. In conclusion,
AZT effectively ameliorates HFD-induced metabolic disorders without inducing mitochondrial toxicity, which

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收稿日期 2025-10-24 通信作者 E-mail：2977035980@qq.com
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E-mail：wangtao1331@cpu.edu.cn