Effects of Xiaozhong Zhitong Mixture （消肿止痛合剂） on Angiogenesis and the Dll4/Notch1 Signaling Pathway in Wound Tissue of Diabetic Foot Ulcer Model Rats
10.13288/j.11-2166/r.2025.16.012
- VernacularTitle:消肿止痛合剂对糖尿病足溃疡模型大鼠创面组织血管生成及Dll4/Notch1信号通路的影响
- Author:
Xiao HAN
1
;
Tao LIU
2
;
Yuan SONG
2
;
Jie CHEN
2
;
Jiaxuan SHEN
2
;
Jing QIAO
3
;
Hengjie WANG
1
;
Lewen WU
1
;
Yazhou ZHAO
1
Author Information
1. Gansu University of Chinese Medicine，Lanzhou，730000
2. Gansu Provincial Hospital of Traditional Chinese Medicine
3. Baotou Mongolian and Traditional Chinese Medicine Hospital
- Publication Type:Journal Article
- Keywords:
Diabetic foot;
ulcer;
angiogenesis;
wound tissue;
Xiaozhong Zhitong Mixture （消肿止痛合剂）;
Delta-like ligand;
Notch1 homolog
- From:
Journal of Traditional Chinese Medicine
2025;66(16):1695-1703
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo investigate the potential machanism of Xiaozhong Zhitong Mixture （消肿止痛合剂， XZM） in the treatment of diabetes foot ulcer （DFU）. MethodsFifty SD rats were randomly divided into blank group， model group， XZM group， inhibitor group， XZM plus inhibitor group （combination group）， with 10 rats in each group. Except for the blank group， rats were fed with high-sugar， high-fat， high-cholesterol diet， intraperitoneally injected with streptozotocin， and subjected to skin defect to establish DFU model. After successful modeling， the XZM group and the combination group were given 1 ml/（100 g·d）of XZM by gavage， while the blank group， model group， and inhibitor group were all given an equal volume of 0.9% sodium chloride injection by gavage. Thirty minutes later， the inhibitor group and the combination group were intraperitoneally injected with 5 mg/（kg·d） of Notch1 inhibitor DAPT. All groups were treated once a day. After 14 days of administration， the skin tissue from the dorsal foot of the blank group rats and wound tissue from the other groups were collected. The pathological changes of granulation tissue in the wound were detected using hematoxylin eosin （HE） staining. The microvascular density （MVD） in wounds was detected through immunohistochemical staining. Real time fluorescence quantitative polymerase chain reaction （RT-PCR） and western blotting were used to detect the mRNA and protein levels of Notch1 homolog （Notch1）， Delta-like ligand 4 （Dll4）， Delta-like ligand 4 （VEGF）， and angiopoietin 2 （Ang-2）， respectively. ResultsHistological results showed that the epidermal structure in the dorsal foot skin tissue of the rats in the blank group was intact. In the wound tissue of the model group， the epidermis exhibited excessive keratinization， vacuolar cytoplasm， and a large number of inflammatory cells infiltrating the tissue， while in the XZM group， a large amount of scab formation was observed in the epidermis， with no significant inflammatory cell infiltration and a noticeable increase in fibroblasts. In the combination group and the inhibitor group， partial epidermal scab formation was observed in the wound tissue with a small amount of inflammatory cell infiltration. Compared to those in the blank group， the MVD in the wound tissue increased in the model group， as well as the mRNA expression and protein levels of Notch1 and Dll4， while VEGFA and Ang-2 mRNA expression and protein levels significantly decreased （P＜0.05 or P＜0.01）. Compared to those in the model group， the MVD in the wound tissue of all medication groups significantly increased， and the mRNA and protein levels of Notch1 and Dll4 decreased， while VEGFA and Ang-2 mRNA expression and protein levels increased （P＜0.05 or P＜0.01）. Compared to the XZM group， the inhibitor group and the combination group showed decreased MVD in wound tissue， increased Notch1 and Dll4 mRNA and protein levels， and decreased expression of VEGFA and Ang-2 mRNA and proteins （P＜0.05 or P＜0.01）. ConclusionXZM can effectively promote wound healing in DFU rats， and its mechanism of action may be related to the inhibition of Dll4/Notch1 signaling pathway in the wound tissue， therey promoting angiogenesis.
