同济大学学报（医学版）2025，Vol.46Issue(6)：819-827,9.DOI:10.12289/j.issn.2097-4345.25172
脂肪来源间充质干细胞通过激活Nrf2/Keap1信号通路缓解化疗诱导的小鼠口腔黏膜炎的机制研究
Mechanistic investigation of adipose-derived mesenchymal stem cells in alleviating chemotherapy-induced oral mucositis in mice by activating the Nrf2/Keap1 signaling pathway
摘要
Abstract
Objective To investigater the therapeutic effects of mouse adipose-derived mesenchymal stem cells(mADSCs)on chemotherapy-induced oral mucositis(CIOM),along with their potential mechanisms.Methods A mouse CIOM model was established by intraperitoneally injecting 5-fluorouracil(5-FU)and chemically damaging the tongue mucosa with 70％acetic acid,followed by the injection of mADSCs into the ulcerated area.Hematoxylin and eosin(H-E)staining was performed to observe histological changes,while qRT-PCR was used to measure the expression of inflammatory cytokines and oxidative stress-related factors.Immunohistochemical staining assessed the expression of oxidative stress-related proteins.Results After local injection of mADSCs,the ulcer area in the experimental group was reduced compared to the control group on the ninth day of the experiment.,along with restoration of the epithelial structure,decreased inflammatory cell infiltration,and lowered expression of interleukin-6(IL-6),and tumor necrosis factor-α(TNF-α),indicating therapeutic effects on CIOM.Additionally,treatment with mADSCs resulted in elevated expression of oxidative stress-related factors heme oxygenase 1(HO-1),superoxide dismutase 1(SOD-1),and Nuclear factor(erythroid-derived 2)-like 2(NFE2L2)(Nrf2)in the lesions,while Kelch-like ECH-associated protein 1(Keap1)expression decreased,indicating that these therapies may alleviate oxidative stress through the Nrf2/Keap1 signaling pathway in the treatment of CIOM.Conclusion This study provides preliminary insights into the roles and mechanisms of mADSCs in treating chemotherapy-induced oral mucositis,offering a theoretical foundation for new treatment strategies for CIOM.关键词
化疗性口腔黏膜炎/5-氟尿嘧啶/间充质干细胞/氧化应激Key words
chemotherapy-induced oral mucositis/5-fluorouracil/mesenchymal stem cells/oxidative stress分类
医药卫生引用本文复制引用
李媛媛,赵琛,朱平怡,陈鑫,陈佳璐,何园..脂肪来源间充质干细胞通过激活Nrf2/Keap1信号通路缓解化疗诱导的小鼠口腔黏膜炎的机制研究[J].同济大学学报（医学版）,2025,46(6):819-827,9.基金项目
国家自然科学基金(82170961,82370970) （82170961,82370970）
