Original Article
Study on the mechanism of shikonin promoting autophagy and accelerating wound healing in diabetic rats through upregulating C-X-C chemokine receptor type 4
Xu Jie, Jin Litai, Wang Tao, Tong Yun, Zhang Fan, Lin Manman, Zhang Zikai
Published 2024-01-20
Cite as Chin J Diabetes Mellitus, 2024, 16(1): 84-91. DOI: 10.3760/cma.j.cn115791-20230919-00174
Abstract
ObjectiveTo investigate whether shikonin can regulate autophagy and promote wound healing in diabetic rats by upregulating C-X-C chemokine receptor type 4 (CXCR4).
MethodsA total of 24 Sprague-Dawley (SD) rats were assigned to control, diabetic, diabetic+Shikonin, and diabetic+Shikonin+sh-CXCR4 groups (6 rats in each group) using random number table method. A diabetic rat model was established by intraperitoneal injection of streptozotocin, and a 1 cm-diameter skin punch was used to create an ulcer model on the back of the rat. Wound healing rates were calculated on days 0, 7, 14, and 21 after wounding. On day 21 after wounding, skin tissues were collected for hematoxylin & eosin and Masson trichrome staining to analyze the pathological changes of the wound. CD31 immunohistochemistry was performed to analyze the microvascular density of the wound and Western blotting was used to detect the expression of CXCR4 and cell autophagy-related proteins microtubule-related proteins light chain 3 (LC3)Ⅱ/LC3Ⅰ, Beclin1, and soluble p62 in the wound tissue. Autophagosomes were observed by transmission electron microscopy. One-way analysis of variance was used for comparison between groups.
ResultsCompared with the control group, the diabetic group had reduced wound healing rate (on day 21: 72.44%±6.21% vs. 93.71%±6.76%), neovascularization, collagen deposition, microvascular density, levels of CXCR4, LC3Ⅱ/LC3Ⅰ, and Beclin, and increased p62 levels in the wound tissue, as well as decreased autophagosomes (P<0.05). Compared with the diabetic group, wound healing rate (on day 21: 86.74%±4.86% vs. 72.44%±6.21%), neovascularization, collagen deposition, microvascular density, levels of CXCR4, LC3Ⅱ/LC3Ⅰ, and Beclin, and autophagosomes were increased, but p62 levels were decreased in the diabetic+Shikonin group (P<0.05). Compared with the diabetic+Shikonin group, the diabetic+Shikonin group had decreased wound healing rate (on day 21: 76.15%±3.85% vs. 86.74%±4.86%), neovascularization, collagen deposition, microvascular density, levels of CXCR4, LC3Ⅱ/LC3Ⅰ, and Beclin, and autophagosomes in the wound tissue, as well as increased p62 levels (P<0.05).
ConclusionShikonin promotes the healing of diabetic ulcer wounds by upregulating CXCR4 expression and activating cell autophagy.
Key words:
Shikonin; C-X-C motif chemokine receptor 4; Diabetic ulcers; Cell autophagy; Wound healing
Contributor Information
Xu Jie
Plastic and Cosmetic Center, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua 321000, China
Jin Litai
Phamaceutical Sciences School of Wenzhou Medical University, Wenzhou 325000, China
Wang Tao
Department of Gastrointestinal Surgery, the First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine, Guangzhou 510080, China
Tong Yun
Plastic and Cosmetic Center, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua 321000, China
Zhang Fan
Department of Dermatology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China
Lin Manman
Plastic and Cosmetic Center, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua 321000, China
Zhang Zikai
Plastic and Cosmetic Center, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua 321000, China
