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白藜芦醇调节环磷酰胺诱导免疫抑制小鼠的肠道屏障功能。

Resveratrol regulates intestinal barrier function in cyclophosphamide-induced immunosuppressed mice.

机构信息

Natural Medicine Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, China.

Key Laboratory of Animal Disease and Human Health of Sichuan Province, Sichuan Agricultural University, Chengdu, China.

出版信息

J Sci Food Agric. 2022 Feb;102(3):1205-1215. doi: 10.1002/jsfa.11458. Epub 2021 Aug 13.

DOI:10.1002/jsfa.11458
PMID:34346509
Abstract

BACKGROUND

Resveratrol, a kind of polyphenolic phytoalexin, can be obtained from numerous natural foods. Although resveratrol is demonstrated to have various bioactivities, little is known about the regulation of intestinal barrier function under immunosuppression. The present study is aimed at investigating the regulatory effect of resveratrol on intestinal barrier function in immunosuppression in mice induced by cyclophosphamide.

RESULTS

The effects of resveratrol on intestinal biological barrier were evaluated by 16S rRNA and metagenome sequencing analysis. The results showed that resveratrol could improve diversity of the intestinal microbiota and intestinal flora structure by increasing the abundance of probiotics, and resveratrol regulated the function of gut microbiota to resist immunosuppression. Resveratrol could significantly upregulate the secretion of secretory immunoglobulin A and promote the transcriptional levels of test cytokines, including tumor necrosis factor α, interferon γ, interleukin 4 and interleukin 6 in jejunum and ileum mucosa, suggesting improved intestinal immune barrier by resveratrol. The mRNA and protein levels of tight junction proteins involved in intestinal physical barrier function, including zonula occludens 1 (ZO-1), claudin 1 and occludin, were increased after resveratrol treatment. The protein levels of toll-like receptor 4 (TLR4), phosphorylation nuclear factor kappa-B (NF-κB-p65) and inhibitor of nuclear factor kappa-B kinase α were decreased by resveratrol treatment when compared with the untreated group, indicating inhibition of the TLR4/NF-ĸB signaling pathway.

CONCLUSION

These results provide new insights into regulation of the intestinal barrier function by resveratrol under immunosuppression and potential applications of resveratrol in recovering intestinal function. © 2021 Society of Chemical Industry.

摘要

背景

白藜芦醇是一种多酚类植物抗毒素,可从多种天然食品中获得。虽然白藜芦醇具有多种生物活性,但对于其在免疫抑制下对肠道屏障功能的调节知之甚少。本研究旨在探讨白藜芦醇对环磷酰胺诱导的免疫抑制小鼠肠道屏障功能的调节作用。

结果

通过 16S rRNA 和宏基因组测序分析评估白藜芦醇对肠道生物屏障的影响。结果表明,白藜芦醇通过增加益生菌的丰度来改善肠道微生物群的多样性和肠道菌群结构,白藜芦醇调节肠道微生物群的功能以抵抗免疫抑制。白藜芦醇可显著上调分泌型免疫球蛋白 A 的分泌,并促进肠和回肠黏膜中测试细胞因子的转录水平,包括肿瘤坏死因子 α、干扰素 γ、白细胞介素 4 和白细胞介素 6,提示白藜芦醇改善了肠道免疫屏障。参与肠道物理屏障功能的紧密连接蛋白,包括闭锁蛋白 1(ZO-1)、闭合蛋白 1 和紧密连接蛋白的 mRNA 和蛋白水平在白藜芦醇处理后增加。与未处理组相比,白藜芦醇处理后 TLR4、磷酸化核因子 kappa-B(NF-κB-p65)和核因子 kappa-B 激酶 α 抑制剂的蛋白水平降低,表明 TLR4/NF-ĸB 信号通路被抑制。

结论

这些结果为白藜芦醇在免疫抑制下调节肠道屏障功能提供了新的见解,并为白藜芦醇在恢复肠道功能方面的潜在应用提供了依据。© 2021 化学工业协会。

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