文章基本信息

标题：Zizhu Ointment Accelerates Wound-Healing of Diabetic Ulcers through Promoting M2 Macrophage Polarization via Downregulating the Notch4 Signaling Pathway
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作者：Renyan Huang ; Xiaoming Hu ; Wenhui Li 等
期刊名称：Computational Intelligence and Neuroscience
印刷版ISSN：1687-5265
电子版ISSN：1687-5273
出版年度：2022
卷号：2022
DOI：10.1155/2022/5173836
语种：English
出版社：Hindawi Publishing Corporation
摘要：Objective. The long-term clinical practice shows that Zizhu ointment (ZZO) is an empirical formula for the treatment of diabetic ulcers (DUs). In this study, we investigated the underlying mechanism of ZZO in the treatment of DU mice. Methods. Through streptozotocin induction and high-fat diet, a DU mouse model was established and ZZO was given for treatment. The activation of Notch4 signaling was examined by immunofluorescence staining, RT-PCR, as well as Western blotting. Flow cytometry was performed to detect the counts of F4/80+ cells, M1 and M2 macrophages, as well as the expression of CD11c, CD206, etc. The role of Notch4 in wound healing in diabetic mice was verified by Notch4 inhibitors and agonists. Results. Accelerated wound healing and decreased expression levels of Notch4 and its target genes and ligands were observed in diabetic mice treated with ZZO. ZZO promoted M2 macrophage polarization, downregulated the expression of proinflammatory factors, and upregulated the levels of anti-inflammatory factors. The same tendency was observed in diabetic mice after treatment with Notch4 inhibitors. Knockout of Notch4 accelerated the wound healing rate as well. Conclusions. ZZO accelerates wound healing of diabetic mice through inhibiting the activation of Notch4 signaling, promoting M2 macrophage polarization, and alleviating inflammation.