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Volume 40 Issue 6
Jun.  2024
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Article Navigation >  CHINESE JOURNAL OF BURNS AND WOUNDS  > 2024  >  40(6): 579-588
Wang BH,Zhang YB,Zhang XP,et al.Effects and mechanism of metformin on the wound healing of full-thickness skin defects in diabetic rats[J].Chin J Burns Wounds,2024,40(6):579-588.DOI: 10.3760/cma.j.cn501225-20231219-00253.
Citation: Wang BH,Zhang YB,Zhang XP,et al.Effects and mechanism of metformin on the wound healing of full-thickness skin defects in diabetic rats[J].Chin J Burns Wounds,2024,40(6):579-588.DOI: 10.3760/cma.j.cn501225-20231219-00253.
shu

Effects and mechanism of metformin on the wound healing of full-thickness skin defects in diabetic rats

doi: 10.3760/cma.j.cn501225-20231219-00253
  • 1.

    School of Basic Medicine, Ningxia Medical University, Yinchuan 750004, China

  • 2.

    Department of Pathology, Xi'an Chest Hospital, Xi'an 710100, China

  • 3.

    Department of Dermatology, General Hospital, Ningxia Medical University, Yinchuan 750004, China

  • 4.

    School of Clinical Medicine, Ningxia Medical University, Yinchuan 750004, China

Funds:

Regional Science Fund Project of National Natural Science Foundation of China 82060155

Ningxia Natural Science Foundation 2022AAC03162

National College Student Innovation and Entrepreneurship Training Program 201810752006, 202210752007

Autonomous Region-Level College Student Innovation and Entrepreneurship Training Program S202310752026, S202310752009

Ningxia Hui Autonomous Region Science and Technology Innovation Team of China NXKJT2019010

More Information
    Abstract
  •   Objective  To investigate the effects and mechanism of metformin on the wound healing of full-thickness skin defects in diabetic rats.  Methods  This study was an experimental study. Eighteen 8-week-old male Sprague Dawley rats were divided into control group, diabetes group, and diabetes+metformin group according to complete random grouping method, with 6 rats in each group. The latter two groups of rats were used to create diabetic models, and then four circular full-thickness skin defect wounds with a diameter of 5 mm were made on the back of 18 rats. Metformin F-127 hydrogel was applied only to the wounds of rats in diabetes+metformin group. The wound healing status on post injury day (POD) 7 and 13 was observed and the wound healing rate was calculated. The wound tissue on POD 7 and 13 was collected for hematoxylin-eosin staining to measure the length of re-epithelialized epidermis and calculate the change rates in diameters of epidermal and dermal wounds, for immunohistochemical staining to detect the relative expressions of keratin 10 and proliferating cell nuclear antigen (PCNA), and for Western blotting to detect the protein expressions of keratin 10 and PCNA. The sample size in all the above experiments was 8 except that in the last experiment was 3. The correlations between the relative expressions of keratin 10 and PCNA in wound tissue in three groups of rats and their wound healing rates, and the correlation between the relative expressions of keratin 10 and PCNA in wound tissue were analyzed.  Results  On POD 7, the wound healing rates of rats in diabetes group and diabetes+metformin group were 81.48% (77.89%, 85.53%) and 93.04% (92.51%, 94.24%), which were significantly lower than 100% (97.17%, 100%) in control group (with Z values of 2.37 and -3.36, respectively, P<0.05); the wound healing rate of rats in diabetes+metformin group was significantly higher than that in diabetes group (Z=3.45, P<0.05). On POD 13, the wound healing rates of rats in control group and diabetes+metformin group were both 100% (100%, 100%), which were significantly higher than 94.47% (90.68%, 99.82%) in diabetes group (with Z values of 2.90 and -2.90, respectively, P<0.05). On POD 7, the change rates in epidermal wound diameter of rats in control group and diabetes+metformin group were significantly higher than that in diabetes group (with Z values of 3.36 and -2.74, respectively, P<0.05). The change rates in dermal wound diameter of rats in the three groups were similar on POD 7 and 13 (P>0.05). The lengths of re-epithelialized epidermis of rats in control group and diabetes+metformin group on POD 13 were significantly longer than that in diabetes group (with Z values of 3.34 and -2.64, respectively, P<0.05). The relative expressions of keratin 10 in wound tissue of rats in diabetes group on POD 7 and 13 were significantly higher than those in control group (with Z values of -3.36 and -3.26, respectively, P<0.05) and diabetes+metformin group (with Z values of 3.36 and 3.15, respectively, P<0.05), and the relative expression of keratin 10 in wound tissue of rats in diabetes+metformin group on POD 7 was significantly lower than that in control group (Z=3.05, P<0.05); the relative expressions of PCNA in wound tissue of rats in diabetes group on POD 7 and 13 were significantly lower than those in control group (with both Z values of 3.36, P<0.05) and diabetes+metformin group (with both Z values of -3.36, P<0.05). The protein expressions of keratin 10 in wound tissue of rats in control group and diabetes+metformin group on POD 7 as well as that in diabetes+metformin group on POD 13 were significantly lower than those in diabetes group (P<0.05), and the protein expressions of PCNA in wound tissue of rats in control group and diabetes+metformin group on POD 7 were significantly higher than that in diabetes group (P<0.05). There was a significant positive correlation between the relative expression of keratin 10 in wound tissue and the wound healing rate in control group and diabetes+metformin group of rats (with r values of 0.78 and 0.71, respectively, P<0.05), there was a significant negative correlation between the relative expression of PCNA in wound tissue and the wound healing rate in diabetes+metformin group of rats (r=-0.60, P<0.05), and there was a significant negative correlation between the relative expressions of PCNA and keratin 10 in wound tissue of rats in diabetes group and diabetes+metformin group (with r values of -0.41 and -0.49, respectively, P<0.05).  Conclusions  The diabetic rats with full-thickness skin defect wound exhibit delayed healing, accompanied by up-regulation of keratin 10 and down-regulation of PCNA in keratinocytes in the wound tissue. Metformin can promote wound healing in diabetic rats with full-thickness skin defects by down-regulating keratin 10 expression and up-regulating PCNA expression in keratinocytes in the wound tissue, and the wound healing rate was positively correlated with the expression of keratin 10 and negatively correlated with the expression of PCNA.

     

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