Medical Laboratory Techniques, Vocational School of Health Services, Istinye University, Istanbul, Turkey.
Department of Medical Biology, Cerrahpasa Medical Faculty, Istanbul University-Cerrahpasa, Istanbul, Turkey.
Mol Biol Rep. 2022 Jan;49(1):73-83. doi: 10.1007/s11033-021-06843-7. Epub 2021 Oct 31.
Diabetic chronic wound, which is one of the diabetic complications caused by hyperglycemia, characterized by prolonged inflammation has become one of the most serious challenges in the clinic. Hyperglycemia during diabetes not only causes prolonged inflammation and delayed wound healing but also modulates the activation of nuclear factor-kappa B (NF-κB) and the expression of matrix metalloproteinases (MMPs). Although metformin is the oldest oral antihyperglycemic drug commonly used for treating type 2 diabetes, few studies have explored the molecular mechanism of its topical effect on wound healing. Therefore, we aimed to investigate the molecular effects of topical metformin application on delayed wound healing, which's common in diabetes.
In this context, we created a full-thickness excisional wound model in Wistar albino rats and, investigated NF-κB p65 DNA-binding activity and expression levels of RELA (p65), MMP2 and MMP9 in wound samples taken on days 0, 3, 7, and 14 from diabetic/non-diabetic rats treated with metformin and saline. As a result of our study, we showed that topically applied metformin accelerates wound healing by suppressing NF-κB p65 activity and diminishing the expression of MMP2 and MMP9.
Diabetic wounds treated with metformin healed even faster than those in the control group that mimicked standard wound healing.
糖尿病慢性创面是由高血糖引起的糖尿病并发症之一，其特征为炎症持续时间延长，已成为临床治疗的最大挑战之一。糖尿病患者的高血糖不仅导致炎症持续时间延长和伤口愈合延迟，还调节核因子-κB（NF-κB）的激活和基质金属蛋白酶（MMPs）的表达。二甲双胍虽然是治疗 2 型糖尿病最常用的传统口服降糖药物，但很少有研究探讨其局部应用于创面愈合的分子机制。因此，我们旨在研究局部应用二甲双胍对糖尿病常见的延迟性创面愈合的分子影响。
在本研究中，我们在 Wistar 白化大鼠上创建了全层切开创面模型，并研究了糖尿病/非糖尿病大鼠在接受二甲双胍和生理盐水治疗后第 0、3、7 和 14 天取自创面的样本中 NF-κB p65 DNA 结合活性和 RELA（p65）、MMP2 和 MMP9 的表达水平。我们的研究结果表明，局部应用二甲双胍通过抑制 NF-κB p65 活性和减少 MMP2 和 MMP9 的表达来加速创面愈合。
与模拟标准创面愈合的对照组相比，接受二甲双胍治疗的糖尿病创面愈合更快。
