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海藻酸寡糖通过调节氧化应激、细胞凋亡和炎症信号通路减轻鼠伤寒沙门氏菌诱导的肝损伤。

Alginate Oligosaccharide Alleviates Salmonella Typhimurium-Induced Liver Injury by Regulating Oxidative Stress, Apoptosis, and Inflammatory Signaling Pathway.

作者信息

Liu Yanan, Zhang Xinyu, Ge Yao, Liu Haozhen, Chen Yinfeng, Yang Yang, Yang Ying, Wu Zhenlong

机构信息

State Key Laboratory of Animal Nutrition and Feeding, Department of Companion Animal Science, China Agricultural University, Beijing, 100193, People's Republic of China.

Beijing Advanced Innovation Center for Food Nutrition and Human Health, China Agricultural University, Beijing, 100193, People's Republic of China.

出版信息

Probiotics Antimicrob Proteins. 2025 Aug 15. doi: 10.1007/s12602-025-10650-y.

Abstract

Alginate oligosaccharide (AOS) is a kind of functional oligosaccharides obtained from the degradation of alginate, which has functional properties such as anti-inflammatory, antibacterial, and antioxidant activity. The aim of this study was to investigate whether AOS could alleviate Salmonella enterica serovar Typhimurium (S. Typhimurium)-induced liver injury. In our study, we found that AOS could alleviate S. Typhimurium-caused weight loss, enlargement of the liver and spleen in mice. In addition, AOS attenuated S. Typhimurium-induced inflammatory response as evidenced by the reduced ratio of AST/ALT, and lower the mRNA levels of Il-6, Il-1β, Tnf-α, Ccl3, and Ccl8. Moreover, AOS reduced HO activity and Ho-1 gene expression. TUNEL staining and Western blot results showed that AOS reduced S. Typhimurium-induced hepatic apoptosis. Further study showed that AOS suppressed S. Typhimurium-induced increase in gene expression levels of Tlr2, Tlr4, and Myd88 as well as protein expression levels of TLR2 and p-NF-κB p65. The 16S rRNA results of colonic contents showed that AOS increased the relative abundance of Lactobacillus and decreased Alistipes, Helicobacter, and Bacteroides. Analyses at the species level showed that the AOS + ST group increased the abundance of Lactobacillus johnsonii (L. johnsonii) and Limosilactobacillus reuteri (formely Lactobacillus reuteri, L. reuteri). In addition, Lactobacillus johnsonii culture supernatant and Limosilactobacillus reuteri culture supernatant partially reduced gene expression levels of pro-inflammatory cytokines and chemokines induced by lipopolysaccharide. In conclusion, the alleviation of S. Typhimurium-induced liver injury by AOS may be related to the reduction of inflammatory response, oxidative stress, apoptosis, and regulation of the gut microbiota.

摘要

海藻酸寡糖(AOS)是一种从海藻酸盐降解获得的功能性寡糖,具有抗炎、抗菌和抗氧化活性等功能特性。本研究的目的是调查AOS是否能减轻鼠伤寒沙门氏菌(S. Typhimurium)诱导的肝损伤。在我们的研究中,我们发现AOS可以减轻鼠伤寒沙门氏菌引起的小鼠体重减轻、肝脏和脾脏肿大。此外,AOS减轻了鼠伤寒沙门氏菌诱导的炎症反应,表现为AST/ALT比值降低,以及Il-6、Il-1β、Tnf-α、Ccl3和Ccl8的mRNA水平降低。此外,AOS降低了HO活性和Ho-1基因表达。TUNEL染色和蛋白质印迹结果表明,AOS减少了鼠伤寒沙门氏菌诱导的肝细胞凋亡。进一步研究表明,AOS抑制了鼠伤寒沙门氏菌诱导的Tlr2、Tlr4和Myd88基因表达水平以及TLR2和p-NF-κB p65蛋白表达水平的增加。结肠内容物的16S rRNA结果表明,AOS增加了乳酸杆菌的相对丰度,降低了别样杆菌属、幽门螺杆菌和拟杆菌属的丰度。在物种水平上的分析表明,AOS+ST组增加了约氏乳杆菌(L. johnsonii)和罗伊氏乳杆菌(原名罗伊氏乳杆菌,L. reuteri)的丰度。此外,约氏乳杆菌培养上清液和罗伊氏乳杆菌培养上清液部分降低了脂多糖诱导的促炎细胞因子和趋化因子的基因表达水平。总之,AOS减轻鼠伤寒沙门氏菌诱导的肝损伤可能与炎症反应、氧化应激、细胞凋亡的减少以及肠道微生物群的调节有关。

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