Recent studies have suggested that long-term application of anti-angiogenic drugs may impair oral mucosal wound healing. This study investigated the effect of sunitinib on oral mucosal healing impairment in mice and the therapeutic potential of Bifidobacterium breve (B. breve). A mouse hard palate mucosal defect model was used to investigate the influence of sunitinib and/or zoledronate on wound healing. The volume and density of the bone under the mucosal defect were assessed by micro-computed tomography (micro-CT). Inflammatory factors were detected by protein microarray analysis and enzyme-linked immunosorbent assay (ELISA). The senescence and biological functions were tested in oral mucosal stem cells (OMSCs) treated with sunitinib. Ligated loop experiments were used to investigate the effect of oral B. breve. Neutralizing antibody for interleukin-10 (IL-10) was used to prove the critical role of IL-10 in the pro-healing process derived from B. breve. Results showed that sunitinib caused oral mucosal wound healing impairment in mice. In vitro, sunitinib induced cellular senescence in OMSCs and affected biological functions such as proliferation, migration, and differentiation. Oral administration of B. breve reduced oral mucosal inflammation and promoted wound healing via intestinal dendritic cells (DCs)-derived IL-10. IL-10 reversed cellular senescence caused by sunitinib in OMSCs, and IL-10 neutralizing antibody blocked the ameliorative effect of B. breve on oral mucosal wound healing under sunitinib treatment conditions. In conclusion, sunitinib induces cellular senescence in OMSCs and causes oral mucosal wound healing impairment and oral administration of B. breve could improve wound healing impairment via intestinal DCs-derived IL-10.

最近的研究表明，长期应用抗血管生成药物可能会损害口腔粘膜伤口的愈合。本研究调查了舒尼替尼对小鼠口腔粘膜愈合损伤的影响以及短双歧杆菌( B. breve ) 的治疗潜力。使用小鼠硬腭粘膜缺损模型来研究舒尼替尼和/或唑来膦酸盐对伤口愈合的影响。通过微型计算机断层扫描（micro-CT）评估粘膜缺损下骨的体积和密度。通过蛋白质微阵列分析和酶联免疫吸附测定（ELISA）检测炎症因子。在用舒尼替尼处理的口腔粘膜干细胞（OMSC）中测试了衰老和生物学功能。使用连接环实验来研究口服短双歧杆菌的效果。使用白细胞介素 10 (IL-10) 中和抗体来证明 IL-10 在源自短双歧杆菌的促愈合过程中的关键作用。结果显示，舒尼替尼导致小鼠口腔粘膜伤口愈合受损。在体外，舒尼替尼诱导 OMSC 细胞衰老并影响增殖、迁移和分化等生物学功能。口服短双歧杆菌可以减少口腔粘膜炎症，并通过肠树突状细胞 (DC) 衍生的 IL-10 促进伤口愈合。IL-10逆转了OMSCs中舒尼替尼引起的细胞衰老，并且IL-10中和抗体阻断了短双歧杆菌在舒尼替尼治疗条件下对口腔粘膜伤口愈合的改善作用。总之，舒尼替尼诱导 OMSC 细胞衰老并导致口腔粘膜伤口愈合受损，口服短双歧杆菌可以通过肠 DC 衍生的 IL-10 改善伤口愈合受损。