Found programs: National Natural Science Foundation of China ( No . 81774051) ; Collaborative Innovation Pro- ject of Anhui Province Universities (No . GXXT-2023-078)
Authors：Yuan Mengru1 , Gui Zhongxuan1 , Wan Xinru1 , Zhang Wenna2 , Chen Yan2 , Zhang Mei 1 , 3
Keywords：armillariella tabescens mycelia polysaccharides; TLR4/MyD88/NF-κB signaling pathway; chemo- therapy-induced intestinal mucositis; 5-fluorouracil; tight junction protein; intestinal barrier function
DOI：10.19405/j.cnki.issn1000-1492.2025.07.016
〔Abstract〕 To investigate whether armillariella tabescens polysaccharides (ATPS) alleviates inflamma- tory responses and tissue damage in 5-fluorouracil ( 5-FU)-induced chemotherapy-induced intestinal mucositis (CIM) by inhibiting the TLR4/MyD88/NF-κB signaling pathway. Methods Thirty 8-weeks-old male C57BL/6J mice were randomly divided into five groups ( n = 6 per group) : control group , model group , and ATPS-treated groups (low , medium , high dose:100 , 200 , 400 mg/kg) . Body weight changes were recorded; Disease activity in- dex (DAI) scores were evaluated; small intestinal length and histopathology were measured; HE staining and his- topathological scoring were performed; immunohistochemistry was used to detect the expression of tight junction pro- teins (ZO-1 , Occludin) in the small intestine; serum levels of inflammatory cytokines interleukin-6 ( IL-6) and tumor necrosis factor-alpha (TNF-α) were analyzed by enzyme-linked immunosorbent assay (ELISA) kit; Western blot was employed to quantify ZO-1 , Occludin , and TLR4/MyD88/NF-κB pathway-related protein TLR4 , MyD88 ,NF-κB p65 , IκBα, p-NF-κB p65 , p-IκBαprotein expression . Results Compared with the control group , mice in the model group exhibited significant reductions in body weight , elevated DAI scores , shortened small intestinal length , increased histopathological scores , marked downregulation of ZO-1 and Occludin expression , and elevated levels of inflammatory cytokines TNF-αand IL-6 . Additionally , protein expression levels of TLR4 , MyD88 , p-NF- κB p65 , and p-IκBαwere significantly upregulated ( all P < 0. 01) . In contrast , mice in ATPS-treated groups showed dose-dependent improvements , attenuated weight loss , reduced DAI scores , restored intestinal length , de- creased histopathological scores , upregulated ZO-1 and Occludin expression , reduced TNF-αand IL-6 levels , and downregulated TLR4 , MyD88 , p-NF-κB p65 , and p-IκBαprotein expression (all P < 0. 01) . Conclusion ATPS alleviates 5-FU-induced CIM by inhibiting the TLR4/MyD88/NF-κB signaling pathway.