腿部静脉性溃疡(VLU)是普遍存在的慢性伤口,治疗选择有限。本研究旨在探讨小檗碱在VLU愈合中增强内皮祖细胞(EPC)功能的潜力。
使用HE染色和ELISA测定评估深静脉血栓形成(DVT)小鼠模型中的组织病理学变化和炎性细胞因子水平。采用荧光素酶报告基因测定来鉴定miR-21-3p和RRAGB靶向关系。EPC增殖,迁移,通过CCK-8、Transwell、和小管形成测定,而mTOR通路和自噬相关蛋白通过免疫荧光染色和免疫印迹分析。
■小檗碱显著改善了EPC功能,如扩散,迁移,和体外试管形成,并在DVT小鼠模型中增强体内EPC介导的伤口愈合。此外,miR-21-3p在VLU患者的EPCs中下调,及其过表达改进了模型EPC功能。机械上,RRAGB,调节mTOR通路,被鉴定为EPCs中潜在的miR-21-3p靶标。RRAGB过表达抑制自噬活性和EPC功能受损。
■小檗碱在改善EPC功能和促进VLU伤口愈合方面显示出希望。小檗碱对miR-21-3p/RRAGB轴的调节可以为管理VLU提供有希望的治疗方法。
UNASSIGNED: Venous leg ulcers (VLUs) are prevalent chronic wounds with limited treatment options. This study aimed to investigate the potential of berberine to enhance endothelial progenitor cell (EPC) function in VLU healing.
UNASSIGNED: Histopathological changes and inflammatory cytokine levels in a deep venous thrombosis (DVT) mouse model were assessed using HE staining and ELISA assays. A luciferase reporter assay was employed to identify the miR-21-3p and RRAGB targeting relationship. EPC proliferation, migration, and tube formation were evaluated through CCK-8, Transwell, and tubule formation assays, while the mTOR pathway and autophagy-related proteins were analyzed by immunofluorescence staining and western blotting.
UNASSIGNED: Berberine significantly improved EPC functions, such as proliferation, migration, and tube formation in vitro, and enhanced in vivo EPC-mediated wound healing in a DVT mouse model. Furthermore, miR-21-3p was downregulated in EPCs from VLU patients, and its overexpression improved model EPC functions. Mechanistically, RRAGB, which regulates the mTOR pathway, was identified as a potential miR-21-3p target in EPCs. Overexpression of RRAGB inhibited autophagic activity and impaired EPC function.
UNASSIGNED: Berberine shows promise in ameliorating EPC function and promoting wound healing in VLUs. The regulation of the miR-21-3p/RRAGB axis by berberine could offer a promising therapeutic approach for managing VLUs.