摘要
本研究以CMP-Neu5Ac羟化酶敲除(cytidine-5’-monophosphate-N-acetylneuraminic acid knockout,Cmah^(-/-))小鼠为对象,将猪颌下腺黏蛋白(porcine submaxillary gland mucin,PSM)中的N-羟乙酰神经氨酸(N-glycolylneuraminic acid,Neu5Gc)添加到小鼠饲料中,饮食干预18周后探究Neu5Gc对Cmah^(-/-)小鼠肝脏中核因子κB(nuclear factor kappa-B,NF-κB)信号通路相关蛋白和血清中白细胞介素(interleukin,IL)-6、IL-1β、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)与血清淀粉样蛋白A(serum amyloid A protein,SAA)以及肠道菌群的影响,并分析不同性别对Neu5Gc致Cmah^(-/-)小鼠炎症的影响。结果表明,与普通对照组相比,PSM中的Neu5Gc激活了NF-κB信号通路,显著增加了雄鼠和雌鼠血清中IL-6、IL-1β、TNF-α和SAA的质量浓度;PSM雄鼠处理组中的Bacteroidetes和Firmicutes的相对丰度比值显著升高,Muribaculaceae和Prevotellaceae显著下降,Clostridia UCG-014和Prevotellaceae_NK3B31_group等与肠道炎症呈正相关菌群的相对丰度显著升高;PSM雌鼠处理组中的肠道菌群的丰富度显著减少,Lachnospiraceae和Oscillospiraceae的相对丰度显著下降。综上,PSM中的Neu5Gc可能通过显著下调相关菌群丰度,促进与肠道炎症呈正相关的菌群生长,导致肠道菌群结构紊乱,激活NF-κB信号通路,增加小鼠血清炎性细胞因子的分泌,从而促进Cmah^(-/-)小鼠体内炎症反应,且其致小鼠炎症受性别因素的影响。本研究阐明了膳食红肉的致炎症反应机制,为人们的饮食健康提供了一定的参考。
In this study,the effect of 18 weeks of dietary supplementation of porcine submaxillary gland mucin(PSM) as an abundant source of N-hydroxyacetylneuraminic acid(Neu5Gc) on the expression of proteins involved in the nuclear factor kappa-B(NF-κB) signaling pathway in the liver,serum interleukin(IL)-6,IL-1β,tumor necrosis factor-alpha(TNF-α),serum amyloid A protein(SAA) and the gut microbiota in cytidine-5'-monophosphate-N-acetylneuraminic acid knockout(Cmah^(-/-)) mice was investigated.Meanwhile,the effect of gender on Neu5Gc-induced inflammation in Cmah^(-/-)mice was analyzed.The results showed that Neu5Gc activated the NF-κB signaling pathway and significantly increased the serum concentration of IL-6,IL-1β,TNF-α and SAA in both male and female mice when compared with normal controls.In the PSM-treated male mice,the ratio of Bacteroidetes to Firmicutes(B/F) significantly increased,the relative abundance of Muribaculaceae and Prevotellaceae significantly decreased,and the relative abundance of Clostridia UCG-014 and Prevotellaceae_NK3B31_group,which are positively associated with intestinal inflammation,significantly increased.In the PSM-treated female mice,the richness of gut microbiota significantly decreased,and so did the relative abundance of Lachnospiraceae and Oscillospiraceae.In conclusion,Neu5Gc in PSM could promote inflammatory responses in Cmah^(-/-)mice through significantly down-regulating the abundance of relevant bacterial communities,facilitating the growth of bacterial communities positively associated with intestinal inflammation,leading to structural disorders of gut microbiota,activating the NF-κB signaling pathway and increasing the secretion of serum inflammatory cytokines,and inflammatory response induced in mice by Neu5Gc was affected by gender.Our study provides a reference for a healthy diet.
作者
贺乐丽
刘楚鑫
肖毅
沈清武
吴艳阳
HE Leli;LIU Chuxin;XIAO Yi;SHEN Qingwu;WU Yanyang(Hunan Province Key Laboratory of Food Science and Biotechnology,School of Food Science and Technology,Hunan Agricultural University,Changsha 410128,China)
出处
《食品科学》
EI
CAS
CSCD
北大核心
2024年第14期103-113,共11页
Food Science
基金
国家自然科学基金面上项目(32072334,31771992)。
关键词
N-羟乙酰神经氨酸
炎性细胞因子
肠道菌群
性别差异
慢性炎症
N-glycolylneuraminic acid
inflammatory cytokines
gut microbiota
sex differences
chronic inflammation