Mechanistic study on the effects of 2'-fucosyllactose in alleviating immune checkpoint inhibitor-induced colitis in mice
DOI：10.3872/j.issn.1007-385x.2025.12.003
- VernacularTitle:2'-岩藻糖基乳糖缓解小鼠免疫检查点抑制剂相关结肠炎的机制研究
- Author:
MO Jinling1
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2
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3
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4
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ZHANG Hongtao2
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2
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3
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4
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HU Nan3
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4
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ZHOU Dong1
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ZHU Aoshuang1
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JIANG Jingting3
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4
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ZHANG Wenting1,3,4
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4
Author Information
1. Central Laboratory of Pediatrics, Changzhou Children's Hospital Affiliated to Nantong University, Changzhou 213003, Jiangsu, China;
2. School of Biotechnology and Bioengineering, Jiangnan University, Wuxi 214122, Jiangsu, China;
3. Department of Tumor Biological Treatment, the Third Affiliated Hospital of Soochow University & Changzhou First People's Hospital, Changzhou 213003, Jiangsu, China;
4. Department of Pharmaceutical Research, Research Institution of Asthma and Bronchitis of Changzhou, Changzhou 213003, Jiangsu, China
- Publication Type:Journal Article
- Keywords:
免疫检查点抑制剂相关结肠炎；2'-岩藻糖基乳糖；转录组测序；人乳寡糖；结肠炎
- From:
Chinese Journal of Cancer Biotherapy
2025;32(12):1228-1235
- CountryChina
- Language:Chinese
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Abstract:
[摘 要] 目的：探究2'-岩藻糖基乳糖（2'-FL）对小鼠免疫检查点抑制剂（ICI）相关结肠炎（ICIC）的作用及其机制。方法：用随机数字表法将BALB/c小鼠随机分为对照组、葡聚糖硫酸钠（DSS）组、ICIC组、ICIC + 2'-FL组。DSS组连续7 d自由摄取含3.5% DSS的饮用水诱导结肠炎；ICIC组在摄取含3.5% DSS的饮用水的同时在实验第0天和第4天通过腹腔注射细胞毒性T淋巴细胞相关抗原4抗体（CTLA⁃4抗体，剂量为150 µg/只）构建ICIC模型；ICIC + 2'-FL组在ICIC造模同时从实验开始每日灌胃给予2'-FL[150 mg/(kg·d）]。统计分析小鼠体质量和疾病活动性评分（DAI）变化。第7天处死小鼠，测量结肠长度，用H-E染色法观察各组结肠组织学形态变化，用免疫组织化学（IHC）法检测CD3+ T细胞和CD19+B细胞在结肠组织中的浸润情况，用转录组学方法对结肠组织进行RNA测序，统计分析各组结肠组织中的差异表达基因（DEG）并进行基因本体论（GO）功能注释和京都基因与基因组百科全书（KEGG）富集分析。结果：与对照组和DSS组比较，ICIC组小鼠体质量明显下降、DAI评分上升、结肠长度更短（均P < 0.05），结肠黏膜完整性受损，呈现典型的溃疡性病变；与ICIC组比较，ICIC + 2'-FL组小鼠体质量下降显著缓解、DAI评分降低，结肠长度恢复（均P < 0.05)。转录组学检测结果显示，与ICIC组相比，2'-FL处理组有51个DEG，GO功能注释和KEGG富集分析提示，2'-FL缓解ICIC样症状与B细胞受体、B细胞增殖调控、炎症反应和修复相关通路的上调有关。结论：人乳寡糖2'-FL可显著缓解ICIC的病理进程，其可能通过B细胞受体相关信号通路及与炎症反应和修复相关通路减轻ICIC小鼠结肠组织的损伤。
- Full text:202601140840089658220251203.pdf
