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丙氨酰-谷氨酰胺(Ala-Gln)通过调节肠道微生物群、PI3K-Akt/NF-κB/STAT3 信号通路和相关肺损伤改善葡聚糖硫酸钠(DSS)诱导的急性结肠炎。

Alanyl-Glutamine (Ala-Gln) Ameliorates Dextran Sulfate Sodium (DSS)-Induced Acute Colitis by Regulating the Gut Microbiota, PI3K-Akt/NF-κB/STAT3 Signaling, and Associated Pulmonary Injury.

机构信息

Clinical Laboratory, Affiliated Zhongshan Hospital of Dalian University, No. 6 Jiefang Street, Dalian 110006 Liaoning, China.

Department of Gastroenterology, The First Affiliated Hospital of China Medical University, No. 155 Nanjing North Street, Shenyang 110001, Liaoning, China.

出版信息

ACS Infect Dis. 2023 Apr 14;9(4):979-992. doi: 10.1021/acsinfecdis.3c00014. Epub 2023 Mar 14.

Abstract

The aim of this study was to investigate the protective effect of alanyl-glutamine (Ala-Gln) on acute colitis complicated by pulmonary injury induced by dextran sulfate sodium (DSS) in C57BL/6 mice. The results showed that Ala-Gln intervention alleviated weight loss, the disease activity index (DAI), colon shortening, and pathological injury and regulated the absolute number of CD4T-cell subsets in mesenteric lymph nodes (MLNs). In addition, Ala-Gln intervention significantly ameliorated the composition of the gut microbiota in mice with DSS- induced acute colitis, significantly decreasing the relative abundance of and increasing the abundances of , , and . Moreover, Ala-Gln treatment significantly inhibited the activation of the PI3K-Akt/NF-κB/STAT3 inflammatory signaling pathways in the colon of mice with DSS-induced acute colitis. Notably, Ala-Gln intervention also alleviated the pulmonary injury as well as the imbalance in levels of CD4T-cell subsets in pulmonary tissue in mice with DSS-induced acute colitis. In conclusion, Ala-Gln alleviates DSS-induced acute colitis by regulating the gut microflora and PI3K-Akt/NF-κB/STAT3 signaling pathways, as well as by alleviating accompanying pulmonary injury.

摘要

本研究旨在探讨丙氨酰-谷氨酰胺(Ala-Gln)对葡聚糖硫酸钠(DSS)诱导 C57BL/6 小鼠急性结肠炎合并肺损伤的保护作用。结果表明,Ala-Gln 干预可减轻体重减轻、疾病活动指数(DAI)、结肠缩短和病理损伤,并调节肠系膜淋巴结(MLN)中 CD4T 细胞亚群的绝对数量。此外,Ala-Gln 干预可显著改善 DSS 诱导的急性结肠炎小鼠的肠道微生物群组成,显著降低相对丰度,增加相对丰度 、 、 。此外,Ala-Gln 治疗可显著抑制 DSS 诱导的急性结肠炎小鼠结肠中 PI3K-Akt/NF-κB/STAT3 炎症信号通路的激活。值得注意的是,Ala-Gln 干预还可减轻 DSS 诱导的急性结肠炎小鼠的肺损伤以及肺组织中 CD4T 细胞亚群的失衡。综上所述,Ala-Gln 通过调节肠道微生物群和 PI3K-Akt/NF-κB/STAT3 信号通路以及减轻伴随的肺损伤来缓解 DSS 诱导的急性结肠炎。

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