南方医科大学学报 ›› 2026, Vol. 46 ›› Issue (7): 1685-1695.doi: 10.12122/j.issn.1673-4254.2026.07.21

• • 上一篇    

丁香酸甲酯通过抑制MAPK通路调控肠上皮细胞凋亡减轻葡聚糖硫酸钠诱导的小鼠结肠炎

张龙涛1,3(), 章雨1, 乔通3, 张可妮1, 尹林1, 黄菊2, 李静1,2, 耿志军2, 胡建国1,2()   

  1. 1.蚌埠医科大学第一附属医院,检验科,安徽 蚌埠 233000
    2.蚌埠医科大学第一附属医院,炎症相关性疾病基础与转化研究安徽省重点实验室,安徽 蚌埠 233000;蚌埠医科大学,安徽 蚌埠 233000
    3.蚌埠医科大学第一附属医院,基础医学院免疫学教研室,安徽 蚌埠 233000
  • 收稿日期:2026-01-30 出版日期:2026-07-20 发布日期:2026-07-20
  • 通讯作者: 胡建国 E-mail:15055561902@163.com;jghu9200@bbmu.edu.cn
  • 作者简介:张龙涛,在读硕士研究生,E-mail:15055561902@163.com
  • 基金资助:
    安徽省卫生健康委科研项目(AHWJ2024Aa40007);安徽省自然科学基金项目(2508085MH227);安徽省临床医学研究转化项目(202427b10020088)

Methyl syringate alleviates DSS-induced colitis in mice by suppressing intestinal epithelial cell apoptosis via inhibiting the MAPK signaling pathway

Longtao ZHANG1,3(), Yu ZHANG1, Tong QIAO3, Keni ZHANG1, Lin YIN1, Ju HUANG2, Jing LI1,2, Zhijun GENG2, Jianguo HU1,2()   

  1. 1.Department of Clinical Laboratory, 2Anhui Provincial Key Laboratory of Basic and Translational Research on Inflammation-Related Diseases, First Affiliated Hospital of Bengbu Medical University, Bengbu 233000, China
    3.Department of Immunology, School of Basic Medical Sciences, Bengbu Medical University, Bengbu 233000, China
  • Received:2026-01-30 Online:2026-07-20 Published:2026-07-20
  • Contact: Jianguo HU E-mail:15055561902@163.com;jghu9200@bbmu.edu.cn

摘要:

目的 探讨丁香酸甲酯(MS)对葡聚糖硫酸钠(DSS)诱导小鼠结肠炎的保护作用及机制。 方法 将24只C57BL/6小鼠随机分为对照组(Con组)、造模组(DSS组)、药物处理组(MS组,100 mg/kg),8只/组。通过检测小鼠体质量、疾病活动度(DAI)评分、结肠长度、HE与AB-PAS染色及组织学评分,评估MS对结肠炎的治疗效果。采用ELISA和RT-qPCR检测结肠炎症因子IL-6、TNF-α和IL-10的表达,免疫组化检测髓过氧化物酶(MPO)在结肠组织中的表达,免疫荧光和Western blotting检测紧密连接蛋白ZO-1、Claudin-1的表达与分布,TUNEL染色检测结肠凋亡细胞。体外采用1% DSS诱导NCM460细胞构建凋亡模型,给予MS(50 μmol/L)干预后,通过流式细胞术检测细胞凋亡。采用网络药理学预测和Western blotting检测分析MS的作用机制。 结果 MS处理改善了DSS引起的小鼠体质量下降、结肠缩短、DAI评分和组织学评分升高,减轻肠绒毛结构损伤,增加杯状细胞数量(P<0.05)。同时MS可下调小鼠肠黏膜组织中IL-6、TNF-α和MPO的表达,并上调IL-10的表达(P<0.05)。免疫荧光与Western blotting表明MS可恢复紧密连接蛋白ZO-1、Claudin-1的表达与分布。TUNEL、流式细胞术及Western blotting结果一致表明,MS在体内外均能显著降低肠上皮细胞的凋亡比例,上调抗凋亡蛋白Bcl-2和XIAP,下调促凋亡蛋白C-Caspase3(P<0.05)。KEGG富集分析提示MAPK通路可能与MS疗效相关。Western blotting进一步证实MS能抑制体内外模型中p-JNK、p-ERK、p-p38的磷酸化水平(P<0.05)。 结论 MS通过减少肠上皮细胞凋亡和改善肠屏障损伤来缓解DSS诱导的小鼠结肠炎,其机制可能与抑制MAPK信号通路的表达有关。

关键词: 炎症性肠病, 丁香酸甲酯, 凋亡, 肠屏障, MAPK通路

Abstract:

Objective To investigate the protective effect of methyl syringate (MS) against dextran sodium sulfate (DSS)‑induced colitis in mice and the underlying mechanism. Methods Twenty-four C57BL/6 mice were random and equally into control group, DSS model group, and MS (100 mg/kg) treatment group. The therapeutic effect of MS on colitis was assessed by measuring changes in body weight, disease activity index (DAI) score and colon length and histopathological examinations with HE and AB-PAS staining. ELISA and RT-qPCR were used to detect the expressions of IL-6, TNF-α, and IL-10 in the colon tissue, and immunohistochemistry, immunofluorescence staining, Western blotting and TUNEL staining were used to detect the expressions of myeloperoxidase (MPO), tight junction proteins ZO-1 and claudin-1, and MAPK pathway proteins as well as cell apoptosis in the colon. In cultured NCM460 cells treated with 1% DSS, the effects of MS (50 μmol/L) treatment on cell apoptosis and expressions of poptosis-related proteins and MAPK pathway proteins were evaluated using flow cytometry and Western blotting. Results MS treatment significantly ameliorated DSS-induced body weight loss, colon shortening, increased DAI score and histological inflammation score, and intestinal pathologies in mice. MS downregulated IL-6, TNF-α, and MPO, upregulated IL-10, and restored the expression and distribution of ZO-1 and claudin-1 in the colon tissue of the mice. In the mouse and cell models, MS treatment significantly reduced apoptosis rate of intestinal epithelial cells, upregulated Bcl-2 and XIAP, and downregulated cleaved caspase-3 expressions. KEGG enrichment analysis suggested a possible association of MAPK pathway with the therapeutic effect of MS, which was confirmed by lowered phosphorylation levels of p-JNK, p-ERK, and p-p38 in both the MS-treated mouse and cell models. Conclusion MS alleviates DSS-induced colitis in mice by reducing intestinal epithelial cell apoptosis and improving intestinal barrier damage possibly by inhibiting the MAPK signaling pathway.

Key words: inflammatory bowel disease, methyl syringate, apoptosis, intestinal barrier, MAPK signaling pathway