人参与乳双歧杆菌协同改善长春瑞滨导致的巨噬细胞免疫抑制

doi:10.16352/j.issn.1001-6325.2026.04.0547

摘要/Abstract

摘要： 目的探讨人参、乳双歧杆菌BL-99及其组合物在长春瑞滨(VNR)诱导免疫抑制状态下对巨噬细胞免疫功能的调节作用,并初步分析其作用机制。方法用长春瑞滨构建低免疫力斑马鱼模型和小鼠巨噬细胞系(RAW264.7)模型。斑马鱼实验中,用转基因荧光斑马鱼观察巨噬细胞数量与吞噬功能的变化。细胞实验中,CCK-8法检测人参、BL-99及其组合物对RAW264.7细胞活力的影响、中性红法检测吞噬功能、DCFH-DA荧光探针法检测细胞内活性氧(ROS)水平、annexin V/PI双染检测凋亡情况及RT-qPCR检测凋亡与吞噬相关基因(Bcl2、caspase3、Msr1、Rac1)表达;同时结合网络药理学预测人参的作用机制。结果与对照组相比,模型组斑马鱼巨噬细胞数量和吞噬功能显著下降(P＜0.001)。与模型组相比,人参与BL-99单独干预均显著提高巨噬细胞数量并增强了吞噬功能(P＜0.001);联合干预组的效果显著优于单药组(P＜0.05)。在RAW264.7细胞实验中,人参、BL-99及联合干预组细胞活力与吞噬功能均显著提高,活性氧水平及凋亡率显著下降(P＜0.01)。RT-qPCR结果显示,人参与BL-99组合可上调Bcl2、Msr1和Rac1表达,下调caspase3表达(P＜0.01)。网络药理分析表明,人参调控低免疫力巨噬细胞功能可能与抗凋亡通路相关。结论人参和乳双歧杆菌BL-99在长春瑞滨诱导的免疫抑制模型中通过减轻氧化应激、调控凋亡及吞噬相关基因表达,协同增强了巨噬细胞免疫功能。

关键词: 人参, 乳双歧杆菌BL-99, 免疫抑制, 巨噬细胞, 网络药理学

Abstract: Objective To investigate the modulatory effects of ginseng, Bifidobacterium lactis BL-99 and their combination on the immune function of macrophages under vinorelbine(VNR)-induced immunosuppression, and to preliminarily explore the underlying mechanisms. Methods Vinorelbine-induced immunosuppressive models were establi-shed in both zebrafish and the murine macrophage cell line RAW264.7. In zebrafish experiments, changes of macrophage number and phagocytic function were observed using transgenic fluorescent zebrafish. In cell experiments, the following assessments were conducted: RAW264.7 cell viability by CCK-8 assay, phagocytic function by neutral red assay, intracellular reactive oxygen species (ROS) levels by DCFH-DA fluorescence probe assay, apoptosis by annexin V/PI double staining, and the expression of apoptosis- and phagocytosis-related genes (Bcl2, caspase3,Msr1, Rac1) by RT-qPCR. Network pharmacology was used to predict the mechanism of ginseng. Results Compared to the control group, the model group showed a significant reduction in macrophage number and phagocyte function (P＜0.001). Both ginseng and BL-99 monotherapies significantly increased the number of macrophages and enhanced phagocytosis (P＜0.001), with the combined intervention group showing stronger effects(P＜0.05). In RAW264.7 cells, compared with the model group, cell viability and phagocytosis were significantly enhanced, reactive oxygen species levels and apoptosis rate was significantly decreased in the ginseng, BL-99 and their combination group(P＜0.01). RT-qPCR results showed that ginseng in combination with BL-99 upregulated the expression of Bcl2, Msr1 and Rac1 and downregulated the expression of caspase3(P＜0.01). Network pharmacological analysis suggested that the modulatory effect of ginseng on macrophage function under immunosuppressive conditions is closely associated with anti-apoptotic signaling pathways. Conclusions Ginseng and Bifidobacterium lactis BL-99 synergistically enhance macrophage immune function in the vinorelbine-induced immunosuppression model by alleviating oxidative stress and regulating the expression of apoptosis- and phagocytosis-related genes.

Key words: ginseng, Bifidobacterium lactis BL-99, immune suppression, macrophage, network pharmacology

中图分类号:

R392.5

苏佳龙, 徐贵川, 郑志昕, 张恩宁, 彭桂英. 人参与乳双歧杆菌协同改善长春瑞滨导致的巨噬细胞免疫抑制[J]. 基础医学与临床, 2026, 46(4): 547-554.

SU Jialong, XU Guichuan, ZHENG Zhixin, ZHANG Enning, PENG Guiying. Ginseng and Bifidobacterium lactis synergistically improve vinorelbine-induced macrophage immunosuppression[J]. Basic & Clinical Medicine, 2026, 46(4): 547-554.

参考文献

[1] 许欣筑, 郭丽娜, 郑康帝, 等. 副干酪乳酪杆菌E6通过其代谢物改善长春瑞滨诱导的斑马鱼免疫抑制[J].南方医科大学学报,2025,45:331-339. doi:10.12122/j.issn.1673-4254.2025.02.14
[2] Wang S, Wei W, Yong H, et al. Synergistic anti-cancer and attenuation effects of thymosin on chemotherapeutic drug vinorelbine in tumor-bearing zebrafish[J].Biomed Pharmacother,2023,162:114633.doi:10.1016/j.biopha.2023.114633.
[3] 石峻岭, 孙宇立, 郑志清, 等. 人参果汁浓缩液对环磷酰胺诱导免疫抑制小鼠免疫功能的影响[J].中国食品卫生杂志,2024,36:377-382.doi:10.13590/j.cjfh.2024.04.002.
[4] 赵雯, 刘伟贤, 张海斌, 等. 乳双歧杆菌BL-99以及副干酪乳酪杆菌ET-22增强小鼠免疫功能的研究[J].中国乳品工业,2021,49:13-18.doi:10.19827/j.issn1001-2230.2021.11.003.
[5] Li T, Rui Z, Mao L, et al. Eight weeks of Bifido-bacterium lactis BL-99 supplementation improves lipid metabolism and sports performance through short-chain fatty acids in cross-country skiers: a preliminary study[J].Nutrients,2023,15:4554.doi:10.3390/nu15214554.
[6] 刘世祥. 益生菌联合人参皂苷Rg3对胃癌术后患者免疫力及术后恢复的影响研究[J].贵州医药,2019,43:573-574.
[7] 史珅, 李昊虬, 王龙, 等.3种乳制品对低免疫力模型斑马鱼免疫功能的影响[J].食品科学,2022,43:113-120.
[8] 徐贵川, 彭桂英, 刘华琛, 等.天然活性原料对低免疫力斑马鱼的免疫增强作用[J].中国乳品工业,2025,53:5-13.
[9] Ju L, Jiang J, Jin Y, et al. Modern immunology is crucial to revealing the biological mechanisms of traditional Chinese medicine[J]. J Tradit Chin Med Sci,2023,10:383-394.doi:https://doi.org/10.1016/j.jtcms.2023.10.001.
[10] Zhao X, Guo X, Pang M, et al. Reductive lipid nanoparticles loaded with vinorelbine inhibit chemotherapy-induced invasion of cancer cells by modulating ENPP2[J].Nano Res,2024,17:2886-2898.doi:10.1007/s12274-023-6030-2.
[11] Wu YW, Lin CF, Lin YS, et al. Autophagy regulates vinorelbine sensitivity due to continued Keap1-mediated ROS generation in lung adenocarcinoma cells[J].Cell Death Discov,2018,4:33.doi:10.1038/s41420-018-0098-6.
[12] 宋志明,余舒杰,焦洁,等. 人参皂苷Rb1减轻人脐静脉内皮细胞氧化损伤[J].基础医学与临床,2020,40:1064-1067.doi:10.16352/j.issn.1001-6325.2020.08.010.
[13] Zhao L, Sui M, Zhang T, et al. The interaction between ginseng and gut microbiota[J].Front Nutr,2023,101301468.doi:10.3389/fnut.2023.1301468.
[14] Zhao SJ, Kong FQ, Jie J, et al. Macrophage MSR1 promotes BMSC osteogenic differentiation and M2-like polarization by activating PI3K/AKT/GSK3β/β-catenin pathway[J].Theranostics,2020,10:17-35.doi:10.7150/thno.36930.
[15] Liang J, Oyang L, Rao S, et al. Rac1, A potential target for tumor therapy[J].Front Oncol,2021,11.doi:10.3389/fonc.2021.674426.