Nursing School, University of Campinas, Campinas, SP, 13084-970, Brazil.
Laboratory of Cell Signaling, University of Campinas, Campinas, SP, 13084-970, Brazil.
Arch Dermatol Res. 2018 May;310(4):363-373. doi: 10.1007/s00403-018-1822-z. Epub 2018 Feb 23.
Recent studies have indicated that systemic topiramate can induce an improvement on the aesthetic appearance of skin scars. Here, we evaluated topical topiramate as an agent to improve wound healing in C57/BL6 mice. Mice were inflicted with a 6.0 mm punch to create two wounds in the skin of the dorsal region. Thereafter, mice were randomly assigned to either vehicle or topical topiramate (20 µl of 2% cream) once a day for 14 days, beginning on the same day as wound generation. We analyzed the wound samples over real-time PCR, Western blotting, and microscopy. There was no effect of the topiramate treatment on the time for complete reepithelization of the wound. However, on microscopic analysis, topiramate treatment resulted in increased granulation tissue, thicker epidermal repair, and improved deposition of type I collagen fibers. During wound healing, there were increased expressions of anti-inflammatory markers, such as IL-10, TGF-β1, and reduced expression of the active form of JNK. In addition, topiramate treatment increased the expression of active forms of two intermediaries in the insulin-signaling pathway, IRS-1 and Akt. Finally, at the end of the wound-healing process, topiramate treatment resulted in increased expression of SOX-2, a transcription factor that is essential to maintain cell self-renewal of undifferentiated embryonic stem cells. We conclude that topical topiramate can improve the overall quality of wound healing in the healthy skin of mice. This improvement is accompanied by reduced expression of markers involved in inflammation and increased expression of proteins of the insulin-signaling pathway.
最近的研究表明，全身性托吡酯可改善皮肤疤痕的美观。在这里，我们评估了局部托吡酯作为改善 C57/BL6 小鼠伤口愈合的药物。用 6.0mm 的打孔器在背部皮肤造成两个伤口。此后，小鼠随机分为 vehicle 或局部托吡酯（2%乳膏 20μl）组，每天一次，共 14 天，从造口当天开始。我们通过实时 PCR、Western blot 和显微镜分析了伤口样本。托吡酯处理对伤口完全上皮化的时间没有影响。然而，在显微镜分析中，托吡酯处理导致肉芽组织增加、表皮修复更厚、I 型胶原纤维沉积改善。在伤口愈合过程中，抗炎标志物如 IL-10、TGF-β1 的表达增加，而 JNK 的活性形式的表达减少。此外，托吡酯处理增加了胰岛素信号通路中的两个中间产物 IRS-1 和 Akt 的活性形式的表达。最后，在伤口愈合过程结束时，托吡酯处理导致转录因子 SOX-2 的表达增加，SOX-2 对于维持未分化胚胎干细胞的细胞自我更新至关重要。我们得出结论，局部托吡酯可改善小鼠健康皮肤的整体伤口愈合质量。这种改善伴随着炎症标志物表达减少和胰岛素信号通路蛋白表达增加。
