Differentiation of myofibroblasts in wounds after topical use of metronidazole: an experimental study.

ABSTRACT Objective: to assess the effects of topical administration of metronidazole on fibroblast differentiation and on wound contraction during experimental secondary intention wound healing in rats. Methods: we submitted 108 rats to a circular wound on the back, 2cm in diameter, and divided them into six groups: control group, with application of saline solution on the wound and five experimental groups, divided according to the concentration of metronidazole solution used (4%, 6%, 8%, 10% and 12%). We changed the dressings daily throughout the trial period, which comprised three stages of analysis: three, seven and 14 days. We evaluated wound contraction by digital planimetry, and identified myofibroblasts and protomyofibroblasts using CD34 and α-SMA immunohistochemistry techniques. Results: wound contraction was not different between the experimental and the control groups. Protomyofibroblasts were significantly more numerous at seven days (p=0.022) in the 4%, 6% and 8% metronidazole groups. After 14 days, in the same groups, myofibroblasts predominated significantly (p=0.01). Conclusion: the topical administration of metronidazole solution in skin wounds healing by secondary intention was able to improve the differentiation of fibroblasts. The contraction phase of wound healing remained unchanged, without significant reduction of the contraction evaluated by digital planimetry. These results can be used in favor of the wound healing process.

摘要

目的：评估甲硝唑局部给药对大鼠实验性二期愈合创面过程中成纤维细胞分化及伤口收缩的影响。

方法：将108只大鼠于背部制作直径2cm的圆形创面，分为6组：对照组（创面外涂生理盐水）及5个实验组，实验组依据所用甲硝唑溶液浓度分为4%、6%、8%、10%、12%组。实验周期内每日更换敷料，整个实验包含3个分析阶段：术后3天、7天及14天。采用数字平面测量法评估伤口收缩情况，通过CD34与α-平滑肌肌动蛋白（α-SMA）免疫组化技术鉴定肌成纤维细胞（myofibroblasts）及前肌成纤维细胞（protomyofibroblasts）。

结果：实验组与对照组的伤口收缩率无显著差异。术后7天，4%、6%、8%甲硝唑组的前肌成纤维细胞数量显著增多（p=0.022）；术后14天，上述浓度组的肌成纤维细胞占比显著升高（p=0.01）。

结论：局部应用甲硝唑溶液可促进大鼠二期愈合皮肤创面的成纤维细胞分化，但伤口愈合的收缩阶段未受显著影响，数字平面测量法评估的伤口收缩率未出现明显降低。本研究结果可为伤口愈合过程提供有益参考。