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Article Navigation >  CHINESE JOURNAL OF BURNS AND WOUNDS  >  > Accepted Manuscript
Shen Qi,Jian Ning,Zhang Cuiping,et al.Effects and mechanisms of broccoli-derived extracellular vesicles on wound healing of full-thickness skin defects in diabetic mice[J].Chin J Burns Wounds,2026,42(6):1-10.DOI: 10.3760/cma.j.cn501225-20260105-00005.
Citation: Shen Qi,Jian Ning,Zhang Cuiping,et al.Effects and mechanisms of broccoli-derived extracellular vesicles on wound healing of full-thickness skin defects in diabetic mice[J].Chin J Burns Wounds,2026,42(6):1-10.DOI: 10.3760/cma.j.cn501225-20260105-00005.
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Effects and mechanisms of broccoli-derived extracellular vesicles on wound healing of full-thickness skin defects in diabetic mice

doi: 10.3760/cma.j.cn501225-20260105-00005

  • Key Laboratory of Wound Repair and Tissue Regeneration, Medical Innovation Research Department, the PLA General Hospital, Beijing 100048, China

Funds:

Integration Program of the Major Research Plan of National Natural Science Foundation of China 92468303

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  • Corresponding author: Fu Xiaobing, Email: fuxiaobing@vip.sina.com
  • Received Date: 2026-01-05
    Available Online: 2026-05-22
    Abstract
  •   Objective  To explore the effects and mechanisms of broccoli-derived extracellular vesicles (BEVs) on wound healing of full-thickness skin defects in diabetic mice.  Methods  This study was an experimental study using a group design and a repeated-measures design. BEVs were isolated and purified using a combination of ultrafiltration concentration and size-exclusion chromatography, and were successfully identified. According to the random number table method, mouse RAW264.7 cells were divided into control group with routine culture, as well as lipopolysaccharide (LPS) group and BEV group, both of which were stimulated with LPS for 12 hours and then respectively subjected to routine culture and culture with BEV. After 24 hours of culture, Western blotting was used to detect the protein expressions of inducible nitric oxide synthase (iNOS) and arginase-1 (Arg-1) in cells. Immunofluorescence method was used to detect the protein expressions of CD86 and CD206 in cells. The level of reactive oxygen species in cells was measured using the 2',7'-dichlorodihydrofluorescein diacetate fluorescence probe assay. The mRNA expressions of nuclear factor E2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) in cells were detected using the real-time fluorescence quantitative reverse transcription polymerase chain reaction method. The sample sizes for all of the above experiments were 3. Twenty-four 7-week-old male db/db mice were used, and a full-thickness skin defect wound was created in the dorsal region. The mice were then assigned to control group and BEV group according to the random number table method, with 12 mice in each group. At post injury day (PID) 0 (immediately), 3, 6, and 9, normal saline and a 1×1010 particles/mL BEVs solution were injected into the wound sites of mice in control group and BEV group, respectively. Wound healing was assessed at PID 0, 3, 6, 9, and 12, and wound healing rates were calculated at PID 3, 6, 9, and 12. At PID 6, the percentages of areas positive for CD86 and CD206 in the wound tissue was assessed using the immunofluorescence method, and the level of reactive oxygen species in the wound tissue was measured using the dihydroethidium fluorescence probe assay.  Results  After 24 hours of culture, compared with those in control group, the protein expressions of iNOS and CD86 of cells in LPS group were significantly elevated (P<0.05), and the level of reactive oxygen species was significantly increased (P<0.05). Compared with those in LPS group, the cells in BEV group showed significantly reduced protein expressions of iNOS and CD86 (P<0.05), significantly increased protein expressions of Arg-1 and CD206 (P<0.05), significantly reduced level of reactive oxygen species (P<0.05), and significantly increased mRNA expressions of Nrf2 and HO-1 (P<0.05). From PID 0 to 12, wounds of mice in both control group and BEV group gradually healed. Specifically, at PID 3, 6, 9, and 12, the wound healing rates of mice in BEV group were significantly higher than those in control group (with t values of 5.98, 5.79, 7.40, and 8.67, respectively, P<0.05). At PID 6, the percentage of the area positive for CD86 in the wound tissue of mice in BEV group was (0.60±0.29)%, which was significantly lower than (1.61±0.19)% in control group (t=7.20, P<0.05); the percentage of the area positive for CD206 in the wound tissue of mice in BEV group was (3.42±0.77)%, which was significantly higher than (0.66±0.20)% in control group (t=8.48, P<0.05); the level of reactive oxygen species in the wound tissue of mice in BEV group was significantly lower than those in control group (t=8.38, P<0.05).  Conclusions  BEVs can restore the "immuno-oxidative" homeostasis of full-thickness skin defect wounds in diabetic mice by activating the Nrf2/HO-1 axis, inducing the polarization of macrophages from the M1 phenotype to the M2 phenotype, and reducing the level of reactive oxygen species, thereby significantly accelerating the wound healing process.

     

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