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- Materials and Methods
- Preparation of a Diabetes Model
- Induction of Skin Damage in Diabetic Rats
- Analysis of Wound Healing
- Hematoxylin-Eosin and Masson’s Trichrome Staining
- Immunohistochemical Analysis for CD68
- Measurement of MMP-9 and TIMP-1 Messenger RNA Levels
- Measurement of MMP-9 and TIMP-1 Protein Contents
- Statistical Analysis
- Results
- Establishment of a Wound Model of Full-Thickness Skin Defect in Streptozotocin-Induced Diabetic Rats
- Comparison of Histopathologic Changes in Different Groups
- Comparison of MMP-9 Messenger RNA and Protein Levels at Different Time Points
- Measurement of TIMP-1 Messenger RNA and Protein Levels
- Comparison of the Ratio of MMP-9 to TIMP-1
- Discussion
- References
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Dynamic Changes in Matrix Metalloproteinase 9 and Tissue Inhibitor of Metalloproteinase 1 Levels During Wound Healing in Diabetic Rats
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Background: We investigated the mechanism of delayed would healing caused by diabetes and measured the dynamic changes in matrix metalloproteinase 9 (MMP-9) and tissue inhibitor of metalloproteinase 1 (TIMP-1) levels. We noted differences in the ratio of MMP-9 to TIMP-1 in the wounds of diabetic and nondiabetic rats.
Methods: Forty-two Sprague-Dawley rats weighing 250 g were randomly assigned to either the control group or the streptozotocin-induced diabetes group. Then, full-thickness excision wounds were created on the middle of the back of each animal. Skin biopsy specimens were obtained on days 0, 3, 7, and 14 after incision. The content of collagen was quantified by Masson’s staining and the macrophage marker, and CD68 was detected by immunohistochemical analysis. Messenger RNA and protein expression of MMP-9 and TIMP-1 was measured by reverse transcriptase–polymerase chain reaction and Western blot, respectively.
Results: Diabetic rats exhibited slower wound healing than control animals (P < .05). On days 3, 7, and 14 after incision, higher levels of MMP-9 messenger RNA and protein expression were detected in the diabetic group compared with the control group (P < .05), and expression of TIMP-1 messenger RNA and protein was significantly decreased. In addition, the ratio of MMP-9 to TIMP-1 was stable in controls, whereas there was a marked increase in the ratio in diabetic skin wounds.
Conclusions: The balance between MMP-9 and its inhibitor, TIMP-1, is disturbed in diabetic skin tissue after injury, which may lead to histologic abnormality of diabetic skin and delayed wound healing. (J Am Podiatr Med Assoc 99(6): 489–496, 2009)
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