饲粮中的萝卜硫素通过REV-ERBα和组蛋白修饰调节猪肝脏抗氧化基因

doi:10.1016/j.jia.2025.02.019

Journal of Integrative Agriculture ›› 2026, Vol. 25 ›› Issue (9): 3814-3828.DOI: 10.1016/j.jia.2025.02.019

饲粮中的萝卜硫素通过REV-ERBα和组蛋白修饰调节猪肝脏抗氧化基因

收稿日期:2024-08-06 修回日期:2025-02-17 接受日期:2024-12-25 出版日期:2026-09-20 发布日期:2026-08-10

Dietary sulforaphane modulates hepatic anti-oxidative genes via REV-ERBα and histone modifications in pigs

Yiting Wang¹, Shicheng Li¹, Yufei Kan¹, Yanli Zhu¹, Kaiqi Li¹, Haoyu Liu^{1, 2}, Tadelle Dessie Alemayehu³, In Ho Kim⁴, Mohammad D. Obeidat⁵, Rui Zhang⁶, Zhaojian Li^1#, Demin Cai¹^,^2#

¹Laboratory of Animal Physiology and Molecular Nutrition, Jiangsu Key Laboratory of Animal Genetic Breeding and Molecular Design, College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, China
²International Joint Research Laboratory in Universities of Jiangsu Province of China for Domestic Animal Germplasm Resources and Genetic Improvement, Yangzhou 225000, China
³ International Livestock Research Institute (ILRI), P.O. Box 5689, Addis Ababa, Ethiopia
⁴ Dankook University, 119, Dandae-ro, Cheonan 31116, Republic of Korea
⁵ Department of Animal Production, Jordan University of Science and Technology (JUST), P.O. Box 3030, 22110 Irbid, Jordan
⁶Meat Processing Key Laboratory of Sichuan Province, College of Food and Biological Engineering, Chengdu University, Chengdu 610106, China

Received:2024-08-06 Revised:2025-02-17 Accepted:2024-12-25 Online:2026-09-20 Published:2026-08-10
About author:Yiting Wang, E-mail: ytwang1631@outlook.com; #Correspondence Demin Cai, E-mail: demincai@yzu.edu.cn; Zhaojian Li, E-mail: 007919@yzu.edu.cn
Supported by:
This work was funded by the National Key R&D Program of China (2023YFD1301200, 2021YFD1300205), the Jiangsu Provincial Double-Innovation Team Program, China (JSSCTD202147), the Natural Science Foundation of Jiangsu Province, China (BK20220582, BK20210812), the Priority Academic Program Development of Jiangsu Higher Education Institutions, China (PAPD), and the Open Project Program of the International Joint Research Laboratory in Universities of Jiangsu Province of China for Domestic Animal Germplasm Resources and Genetic Improvement.

摘要/Abstract

摘要：

萝卜硫素（SFN）是一种在十字花科蔬菜中天然存在的异硫氰酸酯，因其在体内的抗炎和抗氧化效应而受到广泛关注。尽管SFN的健康益处已被广泛认可，但其在动物饲料中添加对猪肝脏健康的影响及其作用机制尚未完全明了。为了探究这一问题，本研究在猪的饲粮中添加了1g kg^-1的SFN，并在50天的饲养周期后对猪的肝脏和血清样本进行了深入分析。研究发现萝卜硫素的添加显著提升了猪的生长性能和肝细胞的增殖能力。此外，SFN还显示出对肝脏健康具有积极影响，它降低了肝脏和血清中的丙二醛（MDA）水平，这是氧化应激的一个重要生物标志物。同时，SFN还增加了肝脏中谷胱甘肽过氧化物酶（GSH-PX）的活性，这是一种关键的抗氧化酶。转录组和蛋白质组学研究表明，SFN下调了包括氧化磷酸化、炎症反应、IL-6-JAK-STAT3信号传导和通过NFκB的TNFα信号传导在内的多个途径。这些途径的下调有助于减轻炎症和氧化应激。同时，它上调了NRF2/GPX4/HO-1的表达，并减少了IL-6和TNFα的表达。这些都是与炎症和氧化应激相关的关键分子。机制研究进一步揭示了SFN可能通过影响NR1D1和NRF2这两个转录因子来调节肝脏中GPX4和HO-1基因的表达。这些基因与抗氧化防御机制密切相关。此外，代谢组分析显示，SFN给药后血清中β-羟丁酸水平下降，这可能与SFN增强了肝脏中赖氨酸β-羟丁酰化（Kbhb）这种表观遗传修饰有关。Kbhb是一种新型的蛋白质修饰方式，其在调控代谢和炎症反应中的作用逐渐受到重视。综上所述，SFN在抵御肝脏炎症和氧化损伤中发挥着保护作用，而且可能通过NRF2和NR1D1的协同作用以及促进肝脏Kbhb的形成来实现这些效果。这些发现为SFN在动物营养和健康领域的应用提供了新的科学依据，但SFN如何促进肝脏Kbhb的形成及其具体机制仍需进一步的研究和探索。

Abstract:

Sulforaphane (SFN) is a naturally occurring isothiocyanate found in cruciferous vegetables known for its anti-inflammatory and antioxidant effects in the body. However, whether its dietary addition impacts porcine liver health remains unclear, and if it does, the mechanisms are unknown. In this study, supplementing the diet of growing pigs with 1 g kg^–1 SFN was found to improve growth performance and hepatocellular proliferation. Further analyses revealed that SFN reduced hepatic and serum malondialdehyde levels, while increasing glutathione peroxidase (GSH-PX) activity in the liver. Transcriptomic and proteomic studies demonstrated that SFN down-regulated multiple pathways, including oxidative phosphorylation, inflammatory responses, IL-6-JAK-STAT3 signaling, and TNFα signaling via NFκB. Meanwhile, it upregulated NRF2/GPX4/HO-1 expression and reduced IL-6 and TNFα expression. Mechanistic studies identified potential NR1D1 and NRF2 binding elements in the promoters of the GPX4 and HO-1 genes in the liver. Furthermore, metabolomic profiling revealed a decline in serum β-hydroxybutyrate levels after the administration of SFN, while further analysis confirmed that SFN enhanced a type of epigenetic modification in the liver, lysine β-hydroxybutyrylation (Kbhb). These results highlight the protective roles of SFN against liver inflammation and oxidative damage, and a novel mechanism involving NRF2 and NR1D1 synergy is proposed, although the promotion of hepatic Kbhb by SFN still requires further exploration.

Key words: sulforaphane , anti-oxidative , NR1D1 , lysine β-hydroxybutyrylatio

Yiting Wang, Shicheng Li, Yufei Kan, Yanli Zhu, Kaiqi Li, Haoyu Liu, Tadelle Dessie Alemayehu, In Ho Kim, Mohammad D. Obeidat, Rui Zhang, Zhaojian Li, Demin Cai. 饲粮中的萝卜硫素通过REV-ERBα和组蛋白修饰调节猪肝脏抗氧化基因[J]. Journal of Integrative Agriculture, 2026, 25(9): 3814-3828.

Yiting Wang, Shicheng Li, Yufei Kan, Yanli Zhu, Kaiqi Li, Haoyu Liu, Tadelle Dessie Alemayehu, In Ho Kim, Mohammad D. Obeidat, Rui Zhang, Zhaojian Li, Demin Cai. Dietary sulforaphane modulates hepatic anti-oxidative genes via REV-ERBα and histone modifications in pigs[J]. Journal of Integrative Agriculture, 2026, 25(9): 3814-3828.

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饲粮中的萝卜硫素通过REV-ERBα和组蛋白修饰调节猪肝脏抗氧化基因

Dietary sulforaphane modulates hepatic anti-oxidative genes via REV-ERBα and histone modifications in pigs

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