Skin Wound Healing In Rats Research Articles

Tissue Extract from Brittle Star Undergoing Arm Regeneration Promotes Wound Healing in Rat.

This study set out to evaluate the wound healing properties of brittle star extracts in vitro and in vivo. Due to the great arm regeneration potential of the brittle star, Ophiocoma cynthiae, the present study aimed to evaluate the wound healing effect of hydroalcoholic extracts of brittle star undergoing arm regeneration in wound healing models. The brittle star samples were collected from Nayband Bay, Bushehr, Iran. After wound induction in the arm of brittle stars, hydroalcoholic extracts relating to different times of arm regeneration were prepared. The GC-MS analysis, in vitro MTT cell viability and cell migration, Western blot, and computational analysis tests were performed. Based on the in vitro findings, two BSEs were chosen for in vivo testing. Macroscopic, histopathological and biochemical evaluations were performed after treatments. The results showed positive proliferative effects of BSEs. Specifically, forty-two compounds were detected in all groups of BSEs using GC-MS analysis, and their biological activities were assessed. The MTT assay showed that the 14 d BSE had a higher proliferative effect on HFF cells than 7 d BSE. The cell migration assay showed that the wound area in 7 d and 14 d BSEs was significantly lower than in the control group. Western blot analysis demonstrated an increase in the expression of proliferation-related proteins. Upon the computational analysis, a strong affinity of some compounds with proteins was observed. The in vivo analysis showed that the evaluation of wound changes and the percentage of wound healing in cell migration assay in the 7 d BSE group was better than in the other groups. Histopathological scores of the 7 d BSE and 14 d BSE groups were significantly higher than in the other groups. In conclusion, the hydroalcoholic extract of O. cynthiae undergoing arm regeneration after 7 and 14 days promoted the wound healing process in the cell and rat skin wound healing model due to their proliferative and migratory biological activity.

Developing hyaluronic acid-proline-ferric ion cross-linked film for efficient wound healing application

A novel cross-linked film dressing that can accelerate wound healing and guard against bacterial infection was presented in this work. The hyaluronic acid-proline-ferric ion (HA-Pro-Fe3+) film was successfully prepared by physically cross-linking method, which the carboxyl groups of the HA and Pro molecules should be in coordination with Fe3+. The HA-Pro-Fe3+ cross-linked film showed three-dimensional porous structure, appropriate water vapor permeability and swelling property, favorable cytocompatibility and hemocompatibility, antibacterial and antioxidative capability. The results of rat skin wound healing confirmed that HA-Pro-Fe3+ film could accelerate epithelial regeneration and collagen deposition, promote angiogenesis and significantly improve skin wound healing. Elisa analysis indicated that HA-Pro-Fe3+ material could down-regulate the expression of IL-6 and TNF-α, and up-regulate the level of TGF-β1 and VEGF. Given its biocompatibility, antibacterial ability, promotion of cell proliferation and angiogenesis, the wide application of HA-Pro-Fe3+ cross-linked film in wound repair would be anticipated.

Injection of stem cells derived from allogeneic adipose tissue, a new strategy for the treatment of diabetic wounds

A diabetic wound is one of the major complications of Diabetes mellitus. Considering the impact of these wounds on the health and quality of life of diabetic patients, the need for a suitable treatment is essential. Adipose-derived stem cells (ASCs) play a role in healing diabetic wounds. The purpose of this study is to examine the effect of ASCs on skin wound healing in diabetic rats. Rats were divided into three groups, diabetics treated with ASCs, non-diabetic, and diabetic (treated with phosphate-buffered saline). Skin wounds and its margin were examined to measure the level of vascular endothelial growth factor (VEGF) and transforming growth factor-beta (TGF-β) and histopathological examinations on three, six, and nine days after wound formation and treatment. As a result, the administration of ASCs can reduce the healing time of skin wounds in diabetic rats by controlling inflammation and increasing angiogenesis.

Effect of Ointment Base on the Skin Wound-Healing Deficits in Streptozotocin-Induced Diabetic Rat.

Wound-healing deficits of the skin, one of the most common complications in patients with diabetes, delay wound healing, significantly reducing the patient's QOL. Therefore, the topical treatment of wound areas with drug-containing ointments and dressings is important. In this study, we investigated the effect of various ointment bases on skin wound healing in normal and streptozotocin-induced diabetic rats (STZ rats). Three ointment bases were used: white ointment (oil-based), absorbent cream (emulsion-based, w/o), and macrogol ointment (water-based). Skin wound healing in STZ rats was delayed compared with that in normal rats. Each of the three ointment bases was applied to the skin wound area in normal rats, and there was no difference in the therapeutic effect. The therapeutic effect of both white ointment and absorbent cream was higher in the STZ rats group than that in the non-treated group, and delayed wound healing was observed in STZ rats treated with macrogol ointment. In conclusion, skin wound healing in STZ rats is affected by the properties of the ointment base, and it is important to use an ointment base that controls the drying of the wound area in STZ rats. These findings provide information for the selection of ointment bases useful for application to skin wounds in patients with diabetes.

Evaluation the effect of formulation made of Talh honey, whey protein and collagen on acute excisional skin wound healing in Wistar male rat

Objectives: This study evaluated the ability of using formulation contains Talh honey, whey protein and collagen on wound healing using animal model.
 Methods: 24 Wistar male rats were divided into four groups of 6 rats each as follow; G1 (not treated), G2 (treated with Manuka honey), G3 (treated with Povidone iodine ointment 5%), and G4 (treated with tested formulation). Excisional wound was induced in rat’s dorsal skin. The duration of the study was 18 days. Morphological and histological examination was performed for all groups.
 Results: The tested formula showed reduction in the duration of the inflammatory phase of wound healing when compared to other groups.
 Conclusion: Results from this study indicated the therapeutic potential of the tested formula, which contains natural component, in wound healing as using other therapeutic products. The tested formula is affordable for wide range of patients. Further studies are required to investigate the different mechanisms behind the therapeutic properties of each treatment.

Evaluation of collagen type I and III, TGF-β1, and VEGF gene expression in rat skin wound healing treated by alginate/chitosan hydrogel containing crocetin

Skin tissue engineering is one of the popular strategies are used to improve the wound healing process. In this study, different concentration of Crocetin (Crot) were loaded into a three-dimensional (3D) alginate (Alg) and chitosan (CS) hydrogel to improve wound healing process. After hydrogel preparation, it is characterized with different experiments such as morphology evolution, water absorption, cumulative release, weight loss, hemo- and cytocompatibility, cell viability, and antibacterial properties. Then, the therapeutic role of the prepared hydrogel was investigated in a full-thickness dermal wound in a rat model with analyzing RNA expression and histology. The results showed that fabricated hydrogels had sufficient porosity and the weight loss test verified the appropriate biodegradability of the prepared hydrogel (about 90% after 14 days) that can release enough of the Crot without any toxicity effect. In addition, the in vivo findings showed that the alginate/chitosan/crocetin 150 µM group had the highest wound closure percentage, re-epithelialization, and gene expression. Furthermore, rt-PCR revealed that 150 µM crocetin increased the expression of Collagen type I, III, VEGF, and TGF-β mRNA. Overall, this research indicates that 3D Alg/CS hydrogels containing 150 µM crocetin may be used in the clinic to treat skin injuries.

Insulin modified Decellularized Adipose Tissue/Tremella Polysaccharide hydrogel loaded with ADSCs for skin wound healing

Full-thickness skin wounds still represent a challenge for clinical treatment. Adipose-derived stem cells (ADSCs) therapy is a promising approach to achieve efficient healing in skin wounds. The excellent cell scaffold can promote proliferation, differentiation and paracrine of ADSCs in wound microenvironment, and is a key factor in ADSCs application. Herein, we first prepared the composite hydrogel with decellularized adipose tissue (DAT) and tremella polysaccharide (TPS), and loaded insulin (INS) into the DAT/TPS composite hydrogel (DAT/TPS-gel) to fabricate an efficient carrier for ADSCs in treating skin wound. Our study showed that INS modified DAT/TPS-gel (INS-DAT/TPS-gel) can promote the proliferation, differentiation and paracrine of ADSCs. INS-DAT/TPS-gel laden with ADSCs (ADSCs/INS-DAT/TPS-gel) effectively facilitated the skin wound healing in SD rats. These findings indicated that INS-DAT/TPS-gel was an effective scaffold for ADSCs transplantation, and ADSCs/INS-DAT/TPS-gel provides a potential strategy for the treatment of skin wounds.

Effects of exosomes derived from fibroblast cells on skin wound healing in Wistar rats

BackgroundThe role of exosomes in areas, such as skin wound healing, have been of consideratble interest recently. However, the effects of exosomes derived mainly from fibroblast cells on wound healing have yet to be documented well. The study aimed to evaluate the effects of exosomes derived from fibroblast cells on wound healing in Wistar rats. MethodsHuman fetal skin was isolated afterward centrifuge, and trypsin 0.1% was added to the cells after removing DPBS from the Falcon tube, and the trypsin was removed. The cells were moved to culture flasks. Then, the secondary culture of Human Fetal Skin Fibroblast was done. The pellets containing exosomes were suspended in PBS, and to achieve purified exosomes, the suspended Exosome were passed through a 0.22 µm filter. The exosome solution was kept at − 20 ºC. In the in vivo phase, 48 male Wistar rats were divided into four groups. Group I, low-dose exosome (LDE) solution (150 μl/day), group II high-dose exosome (HDE) solution (300 μl/day), group III commercially available ointment (positive control (PC)) was topically applied on wounds and group VI without treatment (negative control (NC)). A skin biopsy was taken for histopathological analysis. Wound area, depth of ulcer, degree of granulation, and inflammation were assessed. For histopathological assessment, re-epithelialization, inflammatory cells, granulation tissue, crust formation, and collagen maturation (fibrosis) parameters were evaluated. ResultsForty-eight male Wistar rats were included. The HDE group's showed accelerated healing compared to the NC and PC groups at 9 and 12 days. Inflammation and granulation were higher in the HDE, LDE, and PC groups than in the NC group (p < 0.05). The onset of re-epithelialization and collagen deposition was higher in the LDE, HDE, and PC groups, then on nine and 12-day, gradually maturing and extending through the ulcer (p < 0.05). On day 12, in almost all parameters, the LDE and HDE groups showed improved results compared to NC cases (p < 0.05). ConclusionsThe results showed that the utilization of fibroblast-Exo significantly promoted cutaneous wound healing in a rat full-thickness skin ulcer model. This is a potential innovation for cell-free therapy from fibroblast-Exo as a closed structure similar to human cells.

Genistein, a Soybean Isoflavone, Promotes Wound Healing by Enhancing Endothelial Progenitor Cell Mobilization in Rats with Hemorrhagic Shock.

Severe trauma and hemorrhaging are often accompanied by delayed cutaneous wound healing. Soybean isoflavone is a natural phytoestrogen that has attracted great attention due to its protective effects against various injuries. Endothelial progenitor cells (EPCs) are precursor cells with directional differentiation characteristics. This study is to determine whether genistein (GEN), an isoflavone in soybean products, benefits wound healing in hemorrhagic shock (HS) rats by promoting EPC homing and to investigate the underlying mechanisms. In this study, it isfound that GEN promotes skin wound healing in HS rats, which is due at least partly to the mobilization of endogenous EPCs to the injury site via angiotensin II (Ang-II), stromal cell-derived factor-1alpha (SDF-1α), and transforming growth factor beta(TGF-β) signaling.

Retracted: Porcine Fibrin Sealant Promotes Skin Wound Healing in Rats.

[This retracts the article DOI: 10.1155/2022/5063625.].

Effect of Drugs Based on Silver, Copper, and Zinc Nanoparticles on Skin Wound Healing in Rats

Effect of Drugs Based on Silver, Copper, and Zinc Nanoparticles on Skin Wound Healing in Rats

Enhancing the paracrine effects of adipose stem cells using nanofiber-based meshes prepared by light-welding for accelerating wound healing

The interaction between electrospinning nanomaterials and stem cells to repair damaged tissue mainly focus on manipulating cell viability, proliferation, or paracrine by the materials and their specific topology. In particular, the paracrine products of stem cells influence the behavior of those repairable cells (i.e., epidermal cells, fibroblasts, and endothelial cells) to speed up the repair progress. In this study, a series of nanofiber-based meshes were fabricated by electrospinning and light-welding technology to investigate their impacts on the paracrine behaviors of adipose stem cells (ADSCs) and their performance in accelerating wound healing. We found that the nanofiber-based meshes with varied grid sizes and modified with gelatin nanofibers could regulate the paracrine of ADSCs. As a result, the migration of fibroblasts and endothelial cells as well as angiogenesis was all influenced in vitro. In vivo investigation using rat skin wound healing models also indicated that the nanofiber-based meshes could accelerate wound healing rate, increase the thickness of the regenerated epidermis, and promote type I collagen production and CD31-positive vessel formation in the dermis layer. Taken together, such nanofiber-based meshes provide effective and promising alternatives to design tissue-repair scaffolds involving manipulating stem cell paracrine and wound closure.

Photo-crosslinked GelMA loaded with dental pulp stem cells and VEGF to repair critical-sized soft tissue defects in rats

BackgroundTissue engineering of skin and mucosa is essential for the esthetic and functional reconstruction of individuals disfigured by trauma, resection surgery, or severe burns while overcoming the limited amount of autograft and donor site morbidity. PurposeWe aimed to determine whether a combination of Gelatin-methacryloyl (GelMA) hydrogel scaffold alone or loaded with either dental pulp stem cells (DPSCs) and/or vascular endothelial growth factor (VEGF) could improve skin wound healing in rats. Materials and MethodsFour 10 mm full-thickness skin defects were created on the dorsum of 15 Sprague-Dawley rats. The wounds were treated with GelMA alone, GelMA+DPSCs, or GelMA+DPSCs+VEGF. Unprotected wounds were used as controls. Animals were euthanized at 1-, 2-, and 4 weeks post-surgery, and the healing wounds were harvested for clinical, histological, and RT-PCR analysis. ResultsNo signs of clinical inflammation were observed among all groups. Few and sparse mononuclear inflammatory cells were observed in GelMA+DPSCs and GelMA+DPSCs+VEGF groups at 2 weeks, with complete epithelialization of the wounds. At 4 weeks, the epidermis in GelMA+DPSCs and GelMA+DPSCs+VEGF groups was indistinguishable from the empty defect and GelMA groups. The decrease in cellularity and increase in density of collagen fibers were observed over time in both GelMA+DPSCs and GelMA+DPSCs+VEGF groups but were more evident in the GelMA+DPSCs+VEGF group. The GelMA+DPSCs+VEGF group showed a higher expression of the KER 10 gene at all time points compared with the other groups. Expression of Col1 A1 and TGFβ-1 were not statistically different over time neither among the groups. ConclusionGelMA scaffolds loaded with DPSCs, and VEGF accelerated the re-epithelialization of skin wounds.

Preparation and evaluation of chitosan- and hyaluronic acid-grafted pullulan succinate films for skin wound healing

A novel wound dressing that possesses antibacterial properties and accelerates skin wound repair was developed by physically blending hyaluronic acid-grafted pullulan succinate (HA-st-Pu) with chitosan (CS). The HA-st-Pu polymer was synthesized and characterized, and then CS/HA-st-Pu film dressings were prepared by a freeze-drying method. The novel film wound dressings exhibited a three-dimensional cavity structure under scanning electron microscopy (SEM) and a better swelling ratio than CS, HA and Pu alone, absorbing a large amount of liquid and effectively maintaining the moist environment of the wound. CS/HA-st-Pu materials had no cytotoxicity and increased cell proliferation when coincubated with L929 cells. Moreover, CS/HA-st-Pu wound dressings exhibited a certain antibacterial capability against E. coli and S. aureus. In rat skin wound healing, CS/HA-st-Pu film dressings outperformed both the control and market band-aid groups with respect to the reduction of inflammation and acceleration of wound closure.

Preparation of Transdermal Patch Containing Selenium Nanoparticles Loaded with Doxycycline and Evaluation of Skin Wound Healing in a Rat Model.

The present study aimed to prepare and evaluate a controlled-release system based on a chitosan scaffold containing selenium nanoparticles loaded with doxycycline. Its topical application in skin wound healing in rats was investigated. Therefore, 80 female rats were used and, after creating experimental skin defects on their back, were randomly divided into four equal groups: the control group without any therapeutic intervention; the second group received a chitosan transdermal patch (Ch); the third group received chitosan transdermal patch loaded with selenium nanoparticles (ChSeN), and the last group received chitosan transdermal patch containing selenium nanoparticle loaded by doxycycline (ChSeND). Morphological and structural characteristics of the synthesized patches were evaluated, and in addition to measuring the skin wound area on days 3, 7, and 21, a histopathological examination was performed. On the third day of the study, less hemorrhage and inflammation and more neo-vascularization were seen in the ChSeND group. Moreover, on day 7, less inflammation and collagen formation were recorded in the ChSeN and ChSeND groups than in the other groups. At the same time, more neo-vascularization and re-epithelialization were seen in the ChSeND group on days 7 and 21. In addition, on day 21 of the study, the most collagen formation was in this group. Examination of the wound area also showed that the lowest area belonged to the ChSeND group. The results showed that the simultaneous presence of selenium nanoparticles and doxycycline in the ChSeND group provided the best repair compared to the control, Ch and ChSeN groups.

Keratin-Butyrate Scaffolds Promote Skin Wound Healing in Diabetic Rats Through Down-Regulation of IL-1β and Up-Regulation of Keratins 16 and 17

ABSTRACT Impaired wound healing particularly in diabetics creates a significant healthcare burden. The study aimed to evaluate the effect of keratin-butyrate fibers (FKDP +0.1%NaBu) in a full-thickness skin wound model in 30 diabetic rats. Physicochemical examination showed that the obtained dressing possesses a heterogeneous structure and butyrate was slowly released into the wound. Moreover, the obtained dressing is nontoxic and supports cell growth. In vivo results showed that keratin-butyrate dressing accelerated wound healing on days 4 and 7 post-injury (p < .05). Histopathological and immunofluorescence examination revealed that applied dressing stimulated macrophage infiltration, which favors tissue remodeling and regeneration. The dressing was naturally incorporated into regenerating tissue. The highest mRNA expression level of interleukin 1β (IL-1β) was observed during the first 2 weeks in the control wounds compared to FKDP +0.1%NaBu treated wounds, in which IL-1β was significantly decreased. In FKDP +0.1%NaBu dressed wounds, mRNA expression of IL-10 and VEGF increased significantly (p < .05) from day 14. Keratin-butyrate treated wounds enhanced mRNA expression of keratin 16 and 17 and zonula occludens protein-1 and junctional adhesion molecules (p < .05) on days 14, 21, and 28 post-injuries. Our study showed that keratin butyrate dressing is safe and can efficiently accelerate skin wound healing in diabetic rats.

Scaffolds Based on Silk Fibroin with Decellularized Rat Liver Microparticles: Investigation of the Structure, Biological Properties and Regenerative Potential for Skin Wound Healing.

The development of advanced biomaterials and constructs for accelerated recovery of damaged tissues is a key direction in regenerative medicine. Biocompatible scaffolds based on natural biopolymers are widely used for these tasks. Organ decellularization enables obtaining a cell-free extracellular matrix (ECM) with preserved composition and biological activity. The objectives of the present work were combining these two approaches for the development of a composite scaffold based on silk fibroin and ECM microparticles and assessing its structure, biological properties, and regenerative potential. ECM microparticles were obtained by grinding the decellularized matrix of Wistar rat liver in liquid nitrogen. Scaffolds in the form of films were prepared by the casting method. The sinuous and rough topography of the scaffold surface was assessed by the scanning probe nanotomography (SPNT) technique. The inclusion of ECM microparticles in the composition did not affect the elasticity and tensile strength of the scaffolds. The obtained scaffold was non-toxic to cells, maintained high levels of adhesion and proliferation of mouse 3T3 fibroblast and Hep-G2 cells, and showed high regenerative potential, which was studied in the experimental model of full-thickness rat skin wound healing. The wound healing was accelerated by 1.74 times in comparison with the control.

LPS-pretreatment adipose-derived mesenchymal stromal cells promote wound healing in diabetic rats by improving angiogenesis

Mesenchymal stem cells (MSCs) play a key role in wound healing, and the advantages of pretreated MSCs in wound healing have previously been reported. In the present study, we investigated the impact of LPS pretreated human adipose-derived MSCs on skin wound healing in diabetic rats. We found that some improvements occurred through improving angiogenesis. Then, we scrutinized the impact of lipopolysaccharide (LPS) treatment on human adipose-derived MSCs in a high-glucose (HG) medium, as an in vitro diabetic model. In vivo findings revealed significant improvements in epithelialization and angiogenesis of diabetic wounds which received LPS pre-MSCs. Particularly, LPS pre-MSCs-treated diabetic wounds reached considerably higher percentages of wound closure. Also, the granulation tissue of these wounds had higher pronounced epithelialization and more vascularization compared with PBS-treated and MSCs-treated diabetic ones by CD31, VEGF, CD90, collagen 1, and collagen 3 immunostaining. Western-blots analyses indicated that LPS pre-MSCs led to the upregulation of vascular endothelial growth factor (VEGF) and DNMT1. In addition, significantly higher cell viability (proliferation/colonie), and elevated VEGF and DNMT1 protein expression were observed when MSCs were treated with LPS (10 ng/ml, 6 h) in HG culture media. Based on these findings, it is suggested that LPS pre-MSCs could promote wound repair and skin regeneration, in some major processes, via the improvement of cellular behaviors of MSCs in the diabetic microenvironment. The beneficial advantages of LPS treated with mesenchymal stem cells on wound healing may lead to establishing a novel approach as an alternative therapeutic procedure to cure chronic wounds in diabetic conditions.

Effect of taspine hydrochloride on KGF signal pathway in skin wound healing in rats

Purpose: To investigate the effect of taspine hydrochloride and the regulatory involvement of fibroblast growth factor (FGF) signal on skin wound healing in rats.&#x0D; Methods: Wound model rats were assigned to 3 groups (n = 15 each): untreated control, taspine hydrochloride high-dose treatment, and taspine hydrochloride low-dose treatment groups. Fibroblast growth factor (FGF) and keratinocyte growth factor receptor (KGFR) were determined using qPCR, while immunoblot assay was used to assess protein levels of hepatocyte growth factor (HGF), epidermal growth factor (EGF), transforming growth factor-β1 (TGF-β1), vascular endothelial growth factor (VEGF), interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor (TNF-α) and other inflammatory factors.&#x0D; Results: There were significantly down-regulated levels of KGF, KGFR, TGF-β1, VEGF, EGF, HGF, IL-6, IL-8 and TNF-α in control group on the first day, relative to high- and low-dose taspine hydrochloride treatment groups (p &lt; 0.05). Wound repair took more time in control rats than in the 2 taspine HCL-treatment rats. However, healing time was significantly shorter in rats given higher level of taspine HCL (p &lt; 0.05).&#x0D; Conclusion: Taspine hydrochloride down-regulates the high expression of FGF and inhibits inflammatory response in rats with skin trauma. Moreover, it accelerates skin wound healing. These findings support the clinical application of taspine hydrochloride for skin wound healing.

Effect and mechanisms of Polygonatum kingianum (polygonati rhizome) on wound healing in diabetic rats

Ethnopharmacological relevanceDiabetic dermatopathy is one of the most serious and common complications of diabetes. It has been found that high glucose can lead to abnormal glycometabolism. The skin microenvironment pollution caused by the increase in glucose and the oxidative stress mediated by the deposition of advanced glycation end products can lead to invisible skin injury, and the interaction between them is the key factor that makes the skin wounds of diabetic rats difficult to heal. Therefore, the main task of promoting healing is to reduce blood glucose levels and relieve the deposition of advanced glycation end products. Polygonatum kingianum Collett & Hemsl (PK) of Asparagaceae is planted in Yunnan, China, and is used by the Bai, Hani and Wa nationalities as a traditional medicine for preventing and treating diabetes. Aim of the studyTo study the effects of PK extract on skin wound healing in diabetic rats and to explore the regulatory mechanism of PK on wound microenvironment pollution, the antioxidative stress signaling pathway and latent injury of wound skin tissue. MethodsFirst, wounds were prepared after diabetic rats were given PK extract by gavage for 4 weeks, and then gavage was continued for 2 weeks to observe and calculate the wound healing rate. A scanning electron microscope was used to observe the pathomorphological changes in the skin tissue at the edge of the wound. Western blotting was used to detect protein expression. Immunohistochemistry was used to detect the expression of CD34, AGEs, bFGF and VEGF. The Nrf2/HO-1 signaling pathway in skin tissue was detected by fluorescence quantitative PCR. Serum biochemical indicators and inflammatory cytokine levels were detected by a kit. ResultsAfter PK treatment, the wound healing rate increased significantly (P < 0.001), the infiltration of inflammatory cells in skin tissue of DM lesion rats decreased, the number of new blood vessels increased, and the epidermis and dermis thickened. The content of glucose, AGEs, RAGE protein and RAGE mRNA in skin decreased significantly (P < 0.05, P < 0.01, P < 0.001), while the expression of Nrf2 mRNA, HO-1 mRNA, CD34, bFGF and VEGF increased significantly (P < 0.05, P < 0.01, P < 0.001). The levels of SOD, GSH, MMP-9 and MMP-2 in skin decreased (P < 0.05, P < 0.01, P < 0.001), but the level of TIMP-2 increased (P < 0.001). GSP, GHb and ICAM-1 in plasma decreased (P < 0.05, P < 0.01, P < 0.001), while T-AOC, SOD and FINS increased (P < 0.05, P < 0.01). The levels of MDA, TNF-, IL-6, IL-2 and IFN-γ in plasma and wound skin tissue decreased (P < 0.05, P < 0.01, P < 0.001). ConclusionPK can reduce the infiltration of inflammatory cells and glucose content in the skin tissue at the edge of the wound, reduce inflammatory factors in skin and plasma, and increase angiogenesis, thus improving the wound healing rate. PK can alleviate the microenvironment pollution caused by AGEs and glucose metabolism disorder in diabetic rats and induce antioxidant activity through the Nrf 2/HO-1 signaling pathway, thus reducing oxidative damage and offsetting endogenous skin damage and hidden damage.