世界中医药2025，Vol.20Issue(19)：3424-3432,9.DOI:10.3969/j.issn.1673-7202.2025.19.008
紫朱软膏治疗糖尿病足溃疡增殖期纤维化的作用机制
Mechanism of Zizhu Ointment in Treating Fibrosis During the Proliferative Phase of Diabetic Foot Ulcer
摘要
Abstract
Objective:This study primarily analyzed the protective effect of Zizhu Ointment(ZZO)on regulating proliferative phase fibrosis of diabetic foot ulcer(DFU)through the Notch4 receptor/Delta-like ligand 4(Notch4/DLL4)signaling pathway.Methods:Sixty C57 Black 6(C57 BL/6)mice were randomly divided into six groups using a random number table:control group,model group,recombinant basic fibroblast growth factor(rb-bFGF)group,low-dose ZZO group,medium-dose ZZO group,and high-dose ZZO group.After establishing the DFU mouse model,the mice were treated with daily dressing changes and sacrificed after 10 days for sample collection.The ulcer healing rate in each group was calculated,and histopathological changes were observed under the microscope.Quantitative real-time PCR(qRT-PCR),immunohistochemistry(IHC),and Western blot(WB)assays were performed to detect the expression levels of Notch4 receptor(Notch4),Delta-like ligand 4(DLL4),and fibrosis-related proteins including fi-bronectin(FN),collagen type Ⅰ(COL-1),and alpha-smooth muscle actin(α-SMA)in ulcerated skin tissues.Results:After 10 days of intervention,compared with the model group,the ZZO groups and the rb-bFGF group exhibited higher ulcer healing rates and smaller ulcer areas,with the high-dose ZZO group showing the best performance.Masson staining microscopy revealed increased fi-broblast proliferation,collagen fiber deposition,and improved ulcer healing in all ZZO groups and the rb-bFGF group,with the most pronounced effects observed in the high-dose ZZO group.The results of qRT-PCR and WB analyses showed that,compared with the model group,the expression levels of FN,COL-1,and α-SMA during the proliferative phase of wound healing were higher in all ZZO groups and the rb-bFGF group,with the highest levels observed in the high-dose ZZO group.Conversely,the expression levels of Notch4 and DLL4 were lower in the ZZO and rb-bFGF groups compared with the model group,with the lowest levels found in the high-dose ZZO group.Conclusion:ZZZO enhanced wound fibrosis levels during the proliferative phase in DFU mice through the Notch4/DLL4 signaling pathway.The high-dose ZZO group exhibited slightly better wound healing efficacy compared to the rb-bF-GF group during the proliferative phase of DFU.关键词
Notch4受体/Delta样配体4信号通路/紫朱软膏/糖尿病足溃疡/伤口/增殖期/小鼠/纤维化Key words
Notch4 receptor/Delta-like ligand 4(Notch4/DLL4)signaling pathway/Zizhu Ointment/Diabetic foot ulcer/Wound/Proliferative phase/Mice/Fibrosis分类
医药卫生引用本文复制引用
袁美杰,朱旭莹,樊炜静,胡啸明,孙健,游洋,柳国斌..紫朱软膏治疗糖尿病足溃疡增殖期纤维化的作用机制[J].世界中医药,2025,20(19):3424-3432,9.基金项目
国家自然科学基金面上项目(82274528) （82274528）
上海中医药大学科技发展基金项目(23KFL107) （23KFL107）
