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The mechanism of putridity-resolving and regeneration therapy for promoting the healing of diabetes skin ulcers by regulating wound autophagy
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DOI   10.11656/j.issn.1672-1519.2025.04.14
Key Words   putridity-resolving and regeneration therapy;Xiangqi Shengji Ointment;autophagy;diabetes skin ulcer
Author NameAffiliationE-mail
LI Linlin Department of Surgery of Traditional Chinese Medicine, The Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300250, China  
GUO Jing Department of Dermatology, The First Affiliated Hospital of Zhejiang University of Traditional Chinese Medicine, Hangzhou 310006, China  
ZHU Zhaojun Department of Surgery of Traditional Chinese Medicine, The Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300250, China  
LU Xuya Department of Surgery of Traditional Chinese Medicine, The Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300250, China  
ZHANG Zhaohui Department of Surgery of Traditional Chinese Medicine, The Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300250, China zzh45@aliyun.com 
Abstract
    [Objective] To explore the mechanism of action of the chemo-rot regeneration method to regulate wound autophagy to promote the healing of diabetic skin ulcers. [Methods] Sixty male SD rats were randomly divided into four groups:the model group(MX group),the putrefaction group(HF group),the regeneration group(ZS group),and the putrefaction-regeneration group(HFZS group). The model of diabetic skin ulcers was established by intraperitoneal injection of streptozotocin(STZ),followed by a full-thickness skin incision in diabetic rats,and intramuscular injection of hydrocortisone acetate for three consecutive days after one week of acclimatization feeding. After successful model establishment,wound dressings were changed routinely once daily. The MX group received petroleum jelly-impregnated gauze changes,the HF group received bromelain-soaked gauze changes,the ZS group received topical application of Xiangqi Shengji Ointment,and the HFZS group received a combination of Xiangqi Shengji Ointment and bromelain-soaked gauze changes. At four time points(0,3,7,and 14 days) after the initial dressing change,three rats from each group were randomly selected to observe wound healing. The changes in wound area,wound healing rate,and histopathological staining were assessed. Additionally,the expression of autophagy-related proteins and mRNAs in wound tissues was detected on the 7th day after the initial dressing change. [Results] There was no statistically significant difference between the groups compared with the trabecular area before treatment,and at the 7th and 14th days of treatment,the trabecular area of the HFZS group was significantly smaller than the other 3 groups,and the trabecular healing rate was higher than that of the other 3 groups,with statistically significant differences(P<0.01 or P<0.05). Histopathological staining suggested that all groups showed edema with more inflammatory cell infiltration before treatment,and on the 3rd and 7th days after treatment,the infiltration of inflammatory cells in the trauma tissue of each group gradually decreased,and the edema gradually receded,among which the HFZS group had the best effect,and on the 14th day,the infiltrated inflammatory cells in the HF group and the ZS group were fewer than those in the MX group,while the inflammatory cells in the HFZS group were significantly fewer than those in the other 3 groups,and the granulation was free of edema and more fibroblasts and collagen tissue was seen to be deposited. On the 7th day of treatment,compared with the MX group,the HF group showed no statistically significant difference in Beclin-1 protein and mRNA,increased LC3Ⅰ/Ⅱ protein and mRNA,and decreased P62 protein and mRNA,with a statistically significant difference(P<0.01 or P<0.05),and compared with the HF group,the HSZS group showed increased LC3Ⅰ/Ⅱ protein and mRNA,and decreased P62 protein and mRNA,with a statistically significant difference(P<0.01 or P<0.05). mRNA decreased,and the difference was statistically significant(P<0.01). Compared with the ZS group,LC3Ⅰ/Ⅱ protein and mRNA increased and P62 protein and mRNA decreased in the HSZS group,and the difference was statistically significant(P<0.05). [Conclusion] The putridity-resolving and regeneration therapy can promote the healing of skin ulcers in diabetic rats,and its mechanism of action may be related to its promotion of the activation of the autophagic pathway in the traumatic surface.

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