[1]刘其赞△,贺达,徐凯,等.大黄素调控Notch通路促进糖尿病足溃疡修复的机制研究[J].中国中医骨伤科杂志,2026,34(06):58-66.[doi:10.20085/j.cnki.issn1005-0205.260609]
　LIU Qizan,HE Da,XU Kai,et al.Mechanism of Emodin in Promoting Diabetic Foot Ulcer Repair through Regulation of Notch Signaling Pathway[J].Chinese Journal of Traditional Medical Traumatology & Orthopedics,2026,34(06):58-66.[doi:10.20085/j.cnki.issn1005-0205.260609]
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大黄素调控Notch通路促进糖尿病足溃疡修复的机制研究()

《中国中医骨伤科杂志》[ISSN:1005-0205/CN:42-1340/R]

卷:
第34卷
期数:
2026年06期
页码:
58-66
栏目:
基础研究
出版日期:
2026-06-15

文章信息/Info

Title:
Mechanism of Emodin in Promoting Diabetic Foot Ulcer Repair through Regulation of Notch Signaling Pathway
文章编号:
1005-0205(2026)06-0058-09
作者:
刘其赞1△; 贺达1; 徐凯1; 陈广先1; 郑宁宁1; 夏洪乐1
1河北省沧州中西医结合医院(河北 沧州,061000)
Author(s):
LIU Qizan1△; HE Da1; XU Kai1; CHEN Guangxian1; ZHENG Ningning1; XIA Hongle1
1Cangzhou Hospital of Integrated Traditional Chinese and Western Medicine in Hebei Province,Cangzhou 061000,Hebei China.
关键词:
大黄素;  糖尿病足溃疡;  Notch 信号通路;  创面修复;  剂量依赖性双向调控
Keywords:
emodin;  diabetic foot ulcer;  Notch signaling pathway;  wound repair;  bidirectional regulation
分类号:
R28; R58
DOI:
10.20085/j.cnki.issn1005-0205.260609
文献标志码:
A
摘要:
目的:探讨大黄素通过时序性调控Notch信号通路促进糖尿病足溃疡创面修复的作用机制。方法:构建链脲佐菌素诱导的糖尿病大鼠足溃疡模型,随机分为对照组、模型组、大黄素低/中/高剂量组(20/40/80 mg/kg)及大黄素+DAPT干预组。连续给药14 d,动态监测创面愈合率; 组织学分析肉芽形成与胶原沉积; ELISA检测炎症因子(TNF-α,IL-6)及血管内皮生长因子(VEGF); Western Blot与qPCR评估Notch通路关键分子(Notch1,Hes1)表达。结果:大黄素高剂量组创面愈合率与对照组差异无统计学意义(P>0.05),显著高于其他组,差异有统计学意义(P<0.01),且呈剂量依赖性特征。组织学分析显示其有效抑制炎症浸润,促进胶原有序沉积。动态监测显示,中剂量大黄素在修复早期(第7天)激活Notch通路,促进上皮化; 而高剂量大黄素在修复后期(第14天)抑制Notch过度活化,防止胶原紊乱。分子机制上,大黄素呈现双向调控:中剂量大黄素激活Notch通路加速早期上皮化,高剂量大黄素则抑制Notch过度活化,防止病理性纤维化。DAPT干预部分逆转大黄素疗效,证实Notch通路的核心地位。结论:大黄素通过时序性调控Notch信号通路——早期激活促修复、后期抑制防纤维化,协调炎症消退、血管新生与基质重构,为糖尿病足溃疡精准治疗提供新策略。
Abstract:
Objective:To investigate the mechanism by which emodin promotes diabetic foot ulcer(DFU)healing through temporal regulation of the Notch signaling pathway.Methods:A streptozotocin-induced diabetic rat model with dorsal full-thickness wounds was established.Rats were randomly divided into control,model,low/mid/high-dose emodin(20/40/80 mg/kg),and emodin+DAPT groups.After 14 d of intervention,wound healing rate was dynamically monitored.Histological analysis evaluated granulation formation and collagen deposition.ELISA measured inflammatory cytokines(TNF-α,IL-6)and VEGF.Western Blot and qPCR assessed Notch pathway molecules(Notch1,Hes1).Results:High-dose emodin significantly accelerated wound closure to near-normal levels(P<0.01 vs model),showing dose-dependent efficacy.Histology revealed suppressed inflammation and enhanced collagen organization.Mechanistically,emodin bidirectionally modulated Notch signaling:mid-dose activated Notch to promote early re-epithelialization,while high-dose suppressed pathological overactivation.DAPT co-treatment partially abrogated therapeutic effects,confirming Notch pathway indispensability.Conclusion:Emodin orchestrates inflammation resolution,angiogenesis,and extracellular matrix remodeling by dynamically tuning Notch signaling spatiotemporal dynamics,offering a novel precision strategy for DFU management.

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(收稿日期:2025-09-28)

备注/Memo

备注/Memo:
基金项目:河北省中医药管理局科研计划项目(2025554)
△通信作者 E-mail:lq204yq@163.com
更新日期/Last Update: 2026-06-15