中国组织工程研究

中国组织工程研究 ›› 2026, Vol. 30 ›› Issue (28): 7307-7315.doi: 10.12307/2026.773

• 组织构建实验造模 experimental modeling in tissue construction • 上一篇    下一篇

黄腐酚联合游泳改善代谢相关脂肪性肝病大鼠的肝损伤

王  峥1，吴卫东1，朱敬生2   

  1. 1河南体育学院，河南省郑州市  450044；2上海体育大学运动健康学院，上海市   200438
  • 收稿日期:2025-09-25 修回日期:2025-11-11 出版日期:2026-10-08 发布日期:2026-02-11
  • 通讯作者: 吴卫东，博士，副教授，河南体育学院，河南省郑州市 450044
  • 作者简介:王峥，男，1986年生，河南省鹤壁市人，回族，硕士，讲师，主要从事体育教育训练学方面的研究。
  • 基金资助:
    河南省科技攻关课题(202102310324)，项目负责人：吴卫东

Xanthohumol combined with swimming ameliorates hepatic injury in rats with metabolic associated fatty liver disease

Wang Zheng1, Wu Weidong1, Zhu Jingsheng2   

  1. 1Henan Sport University, Zhengzhou 450044, Henan Province, China; 2School of Exercise and Health, Shanghai University of Sport, Shanghai 200438, China
  • Received:2025-09-25 Revised:2025-11-11 Online:2026-10-08 Published:2026-02-11
  • Contact: Wu Weidong, PhD, Associate professor, Henan Sport University, Zhengzhou 450044, Henan Province, China
  • About author:Wang Zheng, MS, Lecturer, Henan Sport University, Zhengzhou 450044, Henan Province, China
  • Supported by:
    Henan Province Science and Technology Research Project, No. 202102310324 (to WWD)

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摘要：



文题释义：
代谢相关脂肪性肝病：曾称非酒精性脂肪性肝病，与肥胖、胰岛素抵抗等代谢异常相关，以肝细胞内脂肪过度蓄积为特征，可进展为脂肪性肝炎、肝纤维化甚至肝硬化、肝癌，是全球常见的慢性肝病之一。
铁死亡：一种铁依赖的脂质过氧化驱动的细胞程序性死亡方式，区别于凋亡、坏死，核心机制涉及铁代谢紊乱、活性氧积累及脂质过氧化失衡，与代谢相关脂肪性肝病、癌症、神经退行性疾病、缺血再灌注损伤等密切相关。

背景：黄腐酚作为一种天然多酚类物质，具有抗氧化、抗炎等生物活性，近年被发现可能改善脂质代谢紊乱；游泳作为有氧运动，可有效调节机体能量代谢，减轻肝脏脂肪蓄积。但上述二者联合应用对代谢相关脂肪性肝病的干预效果及机制尚未明确。
目的：观察黄腐酚联合游泳对代谢相关脂肪性肝病大鼠核因子E2相关因子2介导的铁死亡通路的影响。
方法：将大鼠随机分为7组，即对照组、模型组、运动组、黄腐酚低、中、高剂量组、联合组，每组12只。对照组大鼠以正常饲料喂养，其他组制备代谢相关脂肪性肝病大鼠模型。运动组和联合组大鼠进行游泳，每天游泳1次，每周游泳6 d，共游泳8周；其他组大鼠安静饲养。黄腐酚低、中、高剂量组分别灌胃2 mL 25，50和100 mg/(kg·d)的黄腐酚；联合组大鼠在游泳训练同时灌胃2 mL 100 mg/(kg·d)的黄腐酚；其他组灌胃2 mL 0.3%羧甲基纤维素钠，共灌胃8周。治疗结束后分别检测各组大鼠血清丙氨酸转氨酶、天门冬氨酸转氨酶和游离脂肪酸含量；通过苏木精-伊红染色观察肝脏脂质积累；按试剂盒说明书检测肝脏丙二醛和还原型谷胱甘肽水平；采用微量法检测肝脏组织亚铁离子含量测量；Western blot检测肝脏组织核因子E2相关因子2、Kelch样ECH相关蛋白1和谷胱甘肽过氧化物酶4蛋白表达；RT-qPCR检测铁死亡相关基因(谷胱甘肽过氧化物酶4、溶质载体家族7成员11、铁蛋白重链1、膜铁转运蛋白1和阳离子转运调控样蛋白1)mRNA水平。
结果与结论：①与运动组和黄腐酚高剂量组比较，联合组大鼠的血清丙氨酸转氨酶、天门冬氨酸转氨酶和游离脂肪酸水平降低，肝脏形态明显改善，肝脏丙二醛水平降低，还原型谷胱甘肽水平升高，肝脏亚铁离子含量降低，肝脏核因子E2相关因子2(细胞核)和谷胱甘肽过氧化物酶4蛋白表达水平升高，Kelch样ECH相关蛋白1蛋白表达水平降低，肝脏谷胱甘肽过氧化物酶4、溶质载体家族7成员11、铁蛋白重链1和膜铁转运蛋白1 mRNA水平升高，阳离子转运调控样蛋白1 mRNA水平降低(P < 0.05)；②提示黄腐酚联合游泳可能通过调控核因子E2相关因子2介导的铁死亡通路改善代谢相关脂肪性肝病大鼠肝损伤。

https://orcid.org/0009-0002-4866-0721(王峥)


中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程

关键词: 代谢相关脂肪性肝病, 黄腐酚, 游泳, 铁死亡, 核因子红细胞2相关因子2

Abstract: BACKGROUND: Xanthohumol is a natural polyphenol that exhibits biological activities such as antioxidant and anti-inflammatory properties. Recently, it has been found to potentially improve lipid metabolism disorders. As an aerobic exercise, swimming can effectively regulate body energy metabolism and reduce hepatic fat accumulation. However, the intervention effect and mechanism of their combined application on metabolic associated fatty liver disease remain unclear.
OBJECTIVE: To investigate the effect of xanthohumol combined with swimming on the ferroptosis pathway mediated by nuclear factor erythroid 2-related factor 2 in rats with metabolic associated fatty liver disease.  
METHODS: Rats were randomly divided into seven groups: control group, model group, exercise group, low-, medium-, and high-dose xanthohumol, and combination groups, with 12 rats in each group. The rats in control group were fed with normal feed, while the rats in other groups were used to prepare metabolic associated fatty liver disease models. Rats in the exercise and combination groups received swimming training once a day, 6 days per week, for a total of 8 weeks. Rats in other groups were raised quietly. Rats in the low-, medium-, and high-dose xanthohumol groups were intragastrically administered 2 mL of xanthohumol at 25, 50, and 100 mg/kg/d, respectively. Rats in the combination group were intragastrically administered 2 mL of xanthohumol at 100 mg/kg/d. Rats in other groups were intragastrically administered 2 mL of 0.3% sodium carboxymethylcellulose. The intragastric administration lasted for 8 weeks. After the treatment, the serum contents of alanine transaminase, aspartate transaminase, and free fatty acids in each group were detected. Hepatic lipid accumulation was observed by hematoxylin-eosin staining. The hepatic levels of malondialdehyde and reduced glutathione were detected according to the kit instructions. The hepatic ferrous ion content was measured by microassay. The protein expression levels of nuclear factor erythroid 2-related factor 2, Kelch-like ECH-associated protein 1, and glutathione peroxidase 4 in liver tissues were detected by Western blot assay. The mRNA expression levels of ferroptosis-related genes (glutathione peroxidase 4, solute carrier family 7 member 11, ferritin heavy chain 1, ferroportin 1, and ChaC aspartate-specific cysteine peptidase 1) were detected by reverse transcription-quantitative polymerase chain reaction.
RESULTS AND CONCLUSION: (1) Compared with the exercise and high-dose xanthohumol groups, the combination group showed decreased serum levels of alanine transaminase, aspartate transaminase, and free fatty acids, significant improvement in liver morphology, reduced hepatic malondialdehyde level, increased hepatic reduced glutathione level, decreased hepatic ferrous ion content, increased protein expression levels of nuclear factor erythroid 2-related factor 2 (in cell nucleus) and glutathione peroxidase 4 in liver tissues, decreased protein expression of Kelch-like ECH-associated protein 1, increased mRNA expression levels of glutathione peroxidase 4, solute carrier family 7 member 11, ferritin heavy chain 1, and ferroportin 1, and decreased mRNA level of ChaC aspartate-specific cysteine peptidase 1 in liver tissues (P < 0.05). (2) These results suggest that xanthohumol combined with swimming may ameliorate liver injury in rats with metabolic associated fatty liver disease by regulating the nuclear factor erythroid 2-related factor 2-mediated ferroptosis pathway.

Key words: metabolic associated fatty liver disease, xanthohumol, swimming, ferroptosis, nuclear factor erythrocyte 2 related factor 2

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