Department of Plastic and Reconstructive Surgery, College of Medicine, The Catholic University of Korea, Seoul, South Korea.
Department of Biomedicine & Health Sciences, College of Medicine, The Catholic University of Korea, Seoul, South Korea.
Int Wound J. 2021 Oct;18(5):647-656. doi: 10.1111/iwj.13566. Epub 2021 Mar 17.
A hypertrophic scar is a common dermal fibroproliferative lesion usually treated with topical silicone. Verapamil, a type of calcium channel blocker, is considered a candidate drug for the treatment of hypertrophic scars. Here, we report that the addition of verapamil to topical silicone gel enhances treatment outcomes of hypertrophic scars. Upon creation of hypertrophic scars with the rabbit ear model, varying concentrations of verapamil-added silicone gel (0.1, 1, and 10 mg/g) were applied daily for 28 days. After the animals were euthanised, microscopic measurement was performed for (a) scar elevation index (SEI), (b) fibroblast count, and (c) capillary count. On gross analysis, features of hypertrophic scars were significantly alleviated in the verapamil-added groups. On histologic examination, verapamil-added groups showed (a) reduced SEI (1.93 (1.79-2.67) for control vs 1.34 (1.21-1.51) for silicone only and 1.13 (1.01-1.65) for verapamil-added silicone), (b) fibroblast count 700.5 (599.5-838.5) for control, 613.25 (461-762.5) for silicone only, and 347.33 (182.5-527) for verapamil-added silicone), and (c) capillary formation (52 (35.5-96.5) for control, 46 (28-64.5) for silicone only, and 39.83(24-70) for verapamil-added silicone) (Kruskal-Wallis test, P < .05). On western blot, expression levels of collagen I protein was lower in the 1 mg/g and 10 mg/g verapamil-added silicone compared with control. Therefore, we suggest a therapeutic concentration of verapamil-added silicone gel of at least over 1 mg/g. Further study regarding maximally effective concentration and deeper insight into the mechanism of action should follow.
增生性瘢痕是一种常见的真皮纤维增生性病变，通常采用局部硅酮治疗。维拉帕米是一种钙通道阻滞剂，被认为是治疗增生性瘢痕的候选药物。在这里，我们报告说，在局部硅酮凝胶中添加维拉帕米可增强增生性瘢痕的治疗效果。通过兔耳模型制造增生性瘢痕后，每天应用不同浓度的添加维拉帕米的硅酮凝胶（0.1、1 和 10 mg/g）28 天。动物安乐死后，对（a）瘢痕隆起指数（SEI）、（b）成纤维细胞计数和（c）毛细血管计数进行显微镜测量。大体分析显示，添加维拉帕米的组明显缓解了增生性瘢痕的特征。组织学检查显示，添加维拉帕米的组显示（a）SEI 降低（对照组为 1.93（1.79-2.67），仅用硅酮组为 1.34（1.21-1.51），添加维拉帕米的硅酮组为 1.13（1.01-1.65）），（b）成纤维细胞计数对照组为 700.5（599.5-838.5），仅用硅酮组为 613.25（461-762.5），添加维拉帕米的硅酮组为 347.33（182.5-527）），和（c）毛细血管形成（对照组为 52（35.5-96.5），仅用硅酮组为 46（28-64.5），添加维拉帕米的硅酮组为 39.83（24-70））（Kruskal-Wallis 检验，P <.05）。在 Western blot 中，与对照组相比，1 mg/g 和 10 mg/g 添加维拉帕米的硅酮中胶原 I 蛋白的表达水平较低。因此，我们建议添加维拉帕米的硅酮凝胶的治疗浓度至少为 1 mg/g 以上。应进一步研究最大有效浓度，并深入了解作用机制。
