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丁香酚通过调节 NF-κB 信号通路缓解传染性胃肠炎病毒诱导的肠上皮损伤。

Eugenol alleviates transmissible gastroenteritis virus-induced intestinal epithelial injury by regulating NF-κB signaling pathway.

机构信息

Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu, China.

Key Laboratory of Animal Disease-resistant Nutrition, Sichuan Agricultural University, Chengdu, China.

出版信息

Front Immunol. 2022 Aug 16;13:921613. doi: 10.3389/fimmu.2022.921613. eCollection 2022.

Abstract

Increasing evidence supports the ability of eugenol to maintain intestinal barrier integrity and anti-inflammatory and ; however, whether eugenol alleviates virus-mediated intestinal barrier damage and inflammation remains a mystery. Transmissible gastroenteritis virus (TGEV), a coronavirus, is one of the main causative agents of diarrhea in piglets and significantly impacts the global swine industry. Here, we found that eugenol could alleviate TGEV-induced intestinal functional impairment and inflammatory responses in piglets. Our results indicated that eugenol improved feed efficiency in TGEV-infected piglets. Eugenol not only increased serum immunoglobulin concentration () but also significantly decreased serum inflammatory cytokine concentration () in TGEV-infected piglets. In addition, eugenol also significantly decreased the expression of mRNA and the phosphorylation level of protein in the jejunum mucosa of TGEV-infected piglets. Eugenol increased villus height and the ratio of villus height to crypt depth in the jejunum and ileum, and decreased serum D-lactic acid levels. Importantly, eugenol increased tight junction protein () and mRNA expression levels of nutrient transporter-related genes ( and ) in the jejunum mucosa of TGEV-infected piglets. Meanwhile, compared with TGEV-infected IPEC-J2 cells, treatment with eugenol reduced the cell cytopathic effect, attenuated the inflammatory response. Interestingly, eugenol did not increase the expression of and in IPEC-J2 cells. However, western blot and immunofluorescence results showed that eugenol restored TGEV-induced down-regulation of ZO-1 and Occludin, while BAY11-7082 (The NF-κB specific inhibitor) enhanced the regulatory ability of eugenol. Our findings demonstrated that eugenol attenuated TGEV-induced intestinal injury by increasing the expression of and , which may be related to the inhibition of signaling pathway. Eugenol may offer some therapeutic opportunities for coronavirus-related diseases.

摘要

越来越多的证据支持丁香酚能够维持肠道屏障的完整性和抗炎作用;然而,丁香酚是否能减轻病毒介导的肠道屏障损伤和炎症仍不清楚。传染性胃肠炎病毒(TGEV),一种冠状病毒,是仔猪腹泻的主要病原体之一,对全球养猪业有重大影响。在这里,我们发现丁香酚可以减轻 TGEV 感染仔猪引起的肠道功能障碍和炎症反应。我们的结果表明,丁香酚可以提高 TGEV 感染仔猪的饲料效率。丁香酚不仅增加了血清免疫球蛋白浓度(),而且还显著降低了 TGEV 感染仔猪的血清炎症细胞因子浓度()。此外,丁香酚还显著降低了 TGEV 感染仔猪空肠黏膜中 mRNA 和蛋白磷酸化水平。丁香酚增加了空肠和回肠的绒毛高度和绒毛高度与隐窝深度的比值,并降低了血清 D-乳酸水平。重要的是,丁香酚增加了 TGEV 感染仔猪空肠黏膜中紧密连接蛋白()和营养转运体相关基因(和)的 mRNA 表达水平。同时,与 TGEV 感染的 IPEC-J2 细胞相比,丁香酚处理降低了细胞病变效应,减轻了炎症反应。有趣的是,丁香酚没有增加 IPEC-J2 细胞中和的表达。然而,Western blot 和免疫荧光结果表明,丁香酚恢复了 TGEV 诱导的 ZO-1 和 Occludin 下调,而 BAY11-7082(NF-κB 特异性抑制剂)增强了丁香酚的调节能力。我们的研究结果表明,丁香酚通过增加和的表达来减轻 TGEV 诱导的肠道损伤,这可能与抑制信号通路有关。丁香酚可能为冠状病毒相关疾病提供一些治疗机会。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/618e/9427193/8dc722aaba28/fimmu-13-921613-g001.jpg

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