摘要
目的:研究2'-岩藻糖基乳糖(2'-FL)、低聚半乳糖(GOS)和低聚果糖(FOS)组合物增强免疫的功能及其最佳作用比例,并探讨其机制。方法:通过免疫抑制斑马鱼模型分析斑马鱼T细胞荧光强度、尾静脉巨噬细胞荧光强度、荧光微球残留数目及肠道黏膜防护功能指标,评价不同比例组合物改善免疫的功效,筛选最佳比例。通过环磷酰胺(CTX)诱导的免疫低下小鼠模型,验证最佳比例组合物对脾脏指数、脾脏T淋巴细胞亚群、免疫脏器病理结构、血清细胞因子、肠道屏障相关蛋白(Claudin-1、ZO-1、Occludin、MUC2)和MAPK信号通路相关蛋白(TLR2,TLR4、p38、ERK1/2、JNK1/2、p65)等免疫指标的影响。结果:2'-FL/GOS/FOS组合物能够显著改善斑马鱼的T细胞减少(P<0.001),促进吞噬细胞功能,改善巨噬细胞减少以及增加肠道杯状细胞数量约23%(P<0.001),最优质量比为2∶3∶3。该最优比例的组合物可以显著提高免疫低下小鼠的脾脏指数(P<0.05),在一定程度上恢复胸腺和脾脏的结构与功能,显著改善CD4^(+)/CD8^(+)淋巴细胞比值(P<0.05),显著降低促炎细胞因子IL-6的浓度(P<0.05),上调肠道屏障相关蛋白Claudin-1及MAPK信号通路相关蛋白TLR4、p38、ERK1/2、JNK1/2、p65的表达(P<0.05)。结论:2'-FL/GOS/FOS组合物可以改善免疫抑制斑马鱼的免疫功能,且组合物质量比为2∶3∶3时功效最佳,还可以显著增强免疫低下小鼠的免疫功能,其机制可能与TLR4受体介导的MAPK和NF-κB信号通路的激活有关。
Objective:To investigate the immunomodulatory effects of a composition of 2'-fucosyllactose(2'-FL),galacto-oligosaccharides(GOS),and fructo-oligosaccharides(FOS),as well as to determine the optimal ratio for enhancing immune function and explore the underlying mechanisms.Methods:An immunosuppressed zebrafish model was employed to analyze T cell fluorescence intensity,the number of fluorescent microspheres retained,fluorescence intensity of tail vein macrophages,and the quantity of intestinal goblet cells.The efficacy of various ratios of the composition in improving immunity was evaluated to identify the optimal proportion.Subsequently,the optimal ratio composition was validated in a cyclophosphamide(CTX)-induced immunocompromised mouse model,assessing its effects on spleen index,morphological changes of immune organs,T lymphocyte subpopulations in the spleen,serum cytokines,and ileal protein related to immune function.Results:The 2'-FL/GOS/FOS composition significantly ameliorated T cell depletion in zebrafish(P<0.001),enhanced phagocytic function,improved macrophage reduction,and increased the number of intestinal goblet cells by about 23%(P<0.001),with the optimal mass ratio determined to be 2∶3∶3.This optimal ratio composition significantly increased the spleen index in immunocompromised mice(P<0.05),partially restored the structure and function of the thymus and spleen,improved the CD4^(+)/CD8^(+)lymphocyte ratio(P<0.05),significantly reduced the concentration of the pro-inflammatory cytokine IL-6(P<0.05),and upregulated the expression of the intestinal barrier-related protein Claudin-1,along with the MAPK signaling pathway-related proteins TLR4,p38,ERK1/2,JNK1/2,and p65(P<0.05).Conclusion:The 2'-FL/GOS/FOS composition could enhance the immune function of immunosuppressed zebrafish.When the composition mass ratio was 2∶3∶3,the efficacy was relatively optimal,significantly boosting immune function in immunocompromised mice.The underlying mechanism might be associated with the activation of the MAPK and NF-κB signaling pathways mediated by TLR4 receptor.
作者
续晓敏
王美华
杨畅
钱文涛
刘思远
李文静
赵艳红
史涵旭
叶湾韵
孟丽苹
许雅君
XU Xiaomin;WANG Meihua;YANG Chang;QIAN Wentao;LIU Siyuan;LI Wenjing;ZHAO Yanhong;SHI Hanxu;YE Wanyun;MENG Liping;XU Yajun(Inner Mongolia Mengniu Dairy(Group)Co.,Ltd.,Hohhot 011500;Mengniu Hi-Tech Dairy Products(Beijing)Co.,Ltd.,Beijing 101100;Department of Nutrition and Food Hygiene,School of Public Health,Peking University,Beijing 100191;Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety,Peking University,Beijing 100191)
出处
《中国食品学报》
北大核心
2025年第11期164-172,共9页
Journal of Chinese Institute of Food Science and Technology
基金
国家重点研发计划“政府间国际科技创新合作”重点专项(2023YFE0114200)。
关键词
母乳低聚糖
低聚半乳糖
低聚果糖
免疫
肠道屏障
human milk oligosaccharides
galacto-oligosaccharides
fructo-oligosaccharides
immunity
intestinal barrier
