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车前草多糖调控TNF-α/NF-κB信号通路和肠道菌群抑制小鼠结肠炎相关结直肠癌的作用研究
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| 篇名： | 车前草多糖调控TNF-α/NF-κB信号通路和肠道菌群抑制小鼠结肠炎相关结直肠癌的作用研究 |
| TITLE： | Study on the inhibitory effects of polysaccharide from Plantago depressa on colitis-associated colorectal cancer in mice by regulating TNF-α/NF-κB signaling pathway and intestinal flora |
| 摘要： | 目的 研究车前草多糖（PLP）对小鼠结肠炎相关结直肠癌（CAC）的抑制作用及机制。方法将小鼠随机分为对照组，模型组，PLP低、中、高剂量组（100、200、400mg/kg），阳性对照组（柳氮磺吡啶，455mg/kg），每组8只。除对照组外，其余各组采用氧化偶氮甲烷+葡聚糖硫酸钠诱导小鼠CAC模型。造模同时，各组小鼠灌胃相应药液，每天1次，连续12周。末次给药后，检测小鼠疾病活动指数（DAI）评分、结肠长度、肿瘤数，观察结肠组织病理学形态，检测血清中炎症因子[白细胞介素1β（IL-1β）、IL-6、干扰素γ（IFN-γ）、肿瘤坏死因子α（TNF-α）]含量，检测结肠组织中TNF-α/核因子κB（NF-κB）信号通路相关蛋白[NF-κBp65、NF-κB抑制蛋白α（IκBα）、NF-κB诱导激酶（NIK）、肿瘤坏死因子受体1（TNFR1）、肿瘤坏死因子受体相关因子2（TRAF2）]表达水平。另外，收集小鼠粪便，通过16SrRNA高通量测序分析肠道菌群结构的变化。结果与模型组比较，PLP各剂量组小鼠DAI评分、肿瘤数和血清中IL-1β、IL-6（低剂量组除外）、IFN-γ、TNF-α含量以及结肠组织中NF-κBp65、IκBα蛋白磷酸化水平和NIK、TNFR1、TRAF2（低剂量组除外）蛋白表达水平均显著降低/减少（P＜0.05），结肠长度显著延长（P＜0.05）；结肠组织可见正常腺体结构，炎症细胞浸润程度减轻，且未发现腺癌形成。肠道菌群分析结果显示，与模型组比较，PLP高剂量组厚壁菌门、梭杆菌门、巨单胞菌属相对丰度均显著降低（P＜0.05），拟杆菌属、阿克曼氏菌属相对丰度以及Shannon、Chao1指数均显著升高（P＜0.05）；PLP调控肠道菌群功能的相关通路主要包括TNF信号通路、Toll样受体信号通路和炎症性肠病信号通路等。结论PLP可能通过抑制TNF-α/NF-κB信号通路活性、调控肠道菌群，发挥抗CAC作用。 |
| ABSTRACT： | OBJECTIVE To study the inhibitory effects of polysaccharide from Plantago depressa （PLP） on colitis-associated colorectal cancer （CAC） in mice and its mechanism. METHODS The mice were randomly divided into control group， model group， PLP low-， medium- and high-dose groups （100， 200， 400 mg/kg）， positive control group （sulfasalazine， 455 mg/kg）， with 8 mice in each group. Except for control group， the remaining groups utilized azomethane oxide + dextran sulfate sodium to induce CAC model. At the same time， mice in each group were administered the corresponding medicinal solution via gavage once daily for 12 consecutive weeks. After the last medication， disease activity index （DAI）， colon length and tumor number were detected； the histopathological morphology of the colon tissue was observed. The levels of inflammatory cytokines [interleukin-1β （IL-1β）， IL-6， interferon-γ （IFN-γ）， and tumor necrosis factor-α （TNF-α）] in the serum were measured. Additionally， the expression levels of proteins related to the TNF-α/nuclear factor-κB （NF-κB） signaling pathway [NF-κB p65， NF-κB inhibitor protein α （IκBα）， NF-κB-inducing kinase （NIK）， tumor necrosis factor receptor 1 （TNFR1）， and tumor necrosis factor receptor-associated factor 2 （TRAF2）] in the colon tissue were detected. In addition， the feces of mice were collected to analyze the changes in intestinal flora composition by 16S rRNA high-throughput sequencing. RESULTS Compared with model group， DAI score， tumor number， serum levels of IL-1β， IL-6 （except for PLP low-dose group）， IFN-γ and TNF-α， as well as phosphorylation levels of IκBα and NF-κB p65 and protein expressions of NIK， TNFR1 and TRAF2 （except for PLP low-dose group） in colon tissue， were all decreased significantly （P＜0.05）； the colon length was significantly increased （P＜0.05）. The colon tissue exhibited normal glandular structures， with a reduced degree of inflammatory E-mail：Ryantang0715@163.com cell infiltration， and no adenocarcinoma formation was observed. The results of gut microbiota analysis revealed that，compared with model group， the relative abundances of Firmicutes， Fusobacteria， and Megamonas in the PLP high-dose group were significantly decreased （P＜0.05）， while the relative abundances of Bacteradetes and Akkermansia， as well as the Shannon and Chao1 indices， were significantly increased （P＜0.05）. The relevant pathways through which PLP regulated intestinal flora function primarily included the TNF signaling pathway， Toll- like receptor signaling pathway， and inflammatory bowel disease signaling pathway， among others. CONCLUSIONS PLP can exert inhibitory effects on CAC by inhibiting TNF-α/NF-κB signaling pathway， and regulating intestinal flora. |
| 期刊： | 2025年第36卷第21期 |
| 作者： | 唐冉；李明 |
| AUTHORS： | TANG Ran，LI Ming |
| 关键字： | 车前草多糖；结直肠癌；TNF-α/NF-κB信号通路；肠道菌群 |
| KEYWORDS： | polysaccharide from Plantago depressa； colon cancer； TNF-α/NF-κB signaling pathway； intestinal flora |
| 阅读数： | 1 次 |
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