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甘氨酸锌通过NrF2/NFκB信号通路减轻脂多糖诱导的鹅肝脏损伤和炎症。

Zn glycine mitigates the LPS-induced hepatic injury and inflammation through NrF2/NFκB signaling in geese.

作者信息

Zulfiqar Zeshan, Asif Muhammad Arslan, Al-Mitib Layla, Alharbi Khawla, Hossain Tanzina, Yao Han, Zhu Xiaoyan, Wang Zhichang, Sun Hao, Cui Yalei, Liu Boshuai, Shi Yinghua

机构信息

Department of Animal Nutrition and Feed Science, College of Animal Science, Henan Agricultural University, Zhengzhou, China.

Department of Biological Sciences, University of Arkansas, Fayetteville, AR 72701, USA.

出版信息

Poult Sci. 2025 Sep 3;104(11):105772. doi: 10.1016/j.psj.2025.105772.

Abstract

Gram-negative bacteria like Escherichia coli have an outer membrane that contains lipopolysaccharide (LPS), which is a powerful inducer of systemic inflammation. It is often associated with gut dysbiosis, intestinal barrier dysfunction, and liver damage. Despite increasing recognition of the gut-liver axis as a critical mediator in systemic inflammation and hepatic pathology, the efficacy of nutritional strategies targeting this pathway remains inadequately defined. This study evaluated the protective effects of zinc glycine (Zn_Gly), a highly bioavailable organic zinc chelate, against LPS-induced gut barrier disruption and liver damage in meat geese. Zn_Gly supplementation @ 80mg/kg of diet significantly attenuated LPS-induced impairments in growth performance, gut morphology, intestinal permeability and liver damage. Zn_Gly reduced considerably (p < 0.01) the levels of LPS in the both liver and ceca, and significantly increased (p<0.01) the expression of tight junction proteins (ZO-1, CLDN-1), thereby mitigating LPS translocation and systemic inflammation (IL-1β, IL-18 and TNF-α) by increasing IL-10 production. Notably, Zn_Gly reversed LPS-mediated oxidative stress by enhancing hepatic antioxidant enzyme activities (SOD, CAT, GSH-Px, T-AOC; p<0.01) and reducing oxidative markers (ROS, MDA, TBARS). Crucially, Zn_Gly mitigated the adverse effects of LPS on liver health by improving ALT, AST, IgG and IgA significantly (p<0.01) leading to reduced Ishaq pathology score and disease related histological parameters. Zn_Gly also improved the hepatic liver metabolism through increasing β-oxidation. Concurrently, Zn_Gly promoted antioxidant defense mechanism NrF2 through upregulation of markers (H0-1, NQO-1 & GCLM). In terms of mechanism, these effects were brought about by blocking the NF-κB signaling pathway, which is essential for the inflammatory liver damage caused by LPS. These findings elucidate Zn_Gly as a promising nutritional modulator of the gut-liver axis, attenuating systemic inflammation and conferring protection against inflammation-induced liver damage. This underscores its therapeutic potential for improving animal health and guiding translational strategies in metabolic disorders associated with gut and hepatic dysfunction.

摘要

像大肠杆菌这样的革兰氏阴性菌有一层外膜,其中含有脂多糖(LPS),它是全身炎症的强力诱导剂。它常与肠道菌群失调、肠道屏障功能障碍和肝损伤相关。尽管人们越来越认识到肠-肝轴是全身炎症和肝脏病理的关键介质,但针对该途径的营养策略的效果仍未得到充分明确。本研究评估了甘氨酸锌(Zn_Gly),一种生物利用率高的有机锌螯合物,对LPS诱导的肉鹅肠道屏障破坏和肝损伤的保护作用。在日粮中添加80mg/kg的Zn_Gly显著减轻了LPS诱导的生长性能、肠道形态、肠道通透性和肝损伤的损害。Zn_Gly显著降低(p < 0.01)肝脏和盲肠中LPS的水平,并显著增加(p<0.01)紧密连接蛋白(ZO-1、CLDN-1)的表达,从而通过增加IL-10的产生减轻LPS易位和全身炎症(IL-1β、IL-18和TNF-α)。值得注意的是,Zn_Gly通过增强肝脏抗氧化酶活性(SOD、CAT、GSH-Px、T-AOC;p<0.01)和减少氧化标志物(ROS、MDA、TBARS)来逆转LPS介导的氧化应激。至关重要的是,Zn_Gly通过显著改善ALT、AST、IgG和IgA(p<0.01)减轻了LPS对肝脏健康的不利影响,导致Ishaq病理评分和疾病相关组织学参数降低。Zn_Gly还通过增加β-氧化改善肝脏代谢。同时,Zn_Gly通过上调标志物(H0-1、NQO-1和GCLM)促进抗氧化防御机制NrF2。在机制方面,这些作用是通过阻断NF-κB信号通路实现的,该信号通路对LPS引起的炎症性肝损伤至关重要。这些发现阐明了Zn_Gly作为肠-肝轴有前景的营养调节剂,减轻全身炎症并对炎症诱导的肝损伤提供保护。这突出了其在改善动物健康以及指导与肠道和肝脏功能障碍相关的代谢紊乱的转化策略方面的治疗潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e85/12464707/defb7b9e02d1/gr1.jpg

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