Department of Dermatology and Allergy, Ludwig Maximilian University, Munich, Germany.
Skin Pharmacol Physiol. 2012;25(6):313-8. doi: 10.1159/000342125. Epub 2012 Aug 31.
Keloids are the result of excessive scar tissue formation. Besides their poor aesthetic appearance, keloids can be associated with severe clinical symptoms such as pain, itching, and rigidity. Unfortunately, most therapeutic approaches remain clinically unsatisfactory. Recently, injections with botulinum toxin A (BTA) were proposed for the treatment of established keloids in a clinical trial. In this study, we aimed to verify the effects of intralesional BTA for the treatment of therapy-resistant keloids using objective measurements. In addition, the underlying molecular mechanisms were investigated using cultured keloid-derived fibroblasts.
Four patients received BTA (doses varying from 70 to 140 Speywood units per session) injected directly into their keloids every 2 months for up to 6 months. Differences in height and volume were evaluated clinically and measured with a 3-D optical profiling system. Keloid-derived fibroblasts were treated with different concentrations of BTA, and expression of collagen (COL)1A1, COL1A2, COL3A1, TGF-β1, TGF-β2, TGF-β3, fibronectin-1, laminin-β2, and α-SMA was determined by real-time quantitative PCR. MTT and BrdU assays were used to analyze the effects of BTA on fibroblast proliferation and metabolism.
Intralesional administration of BTA did not result in regression of keloid tissue. No differences in expression of ECM markers, collagen synthesis, or TGF-β could be observed after BTA treatment of keloid fibroblasts. In addition, cell proliferation and metabolism of keloid fibroblasts was not affected by BTA treatment.
The suggested clinical efficiency of intralesional BTA for the therapy of existent keloids could not be confirmed in this study. Based on our data, the potential mechanisms of action of BTA on keloid-derived fibroblasts remain unclear.
瘢痕疙瘩是过度的疤痕组织形成的结果。除了外观不佳外，瘢痕疙瘩还可能伴有严重的临床症状，如疼痛、瘙痒和僵硬。不幸的是，大多数治疗方法仍不尽如人意。最近，肉毒毒素 A（BTA）的注射被提议用于临床试验中治疗已确立的瘢痕疙瘩。在这项研究中，我们旨在使用客观测量来验证 BTA 对治疗难治性瘢痕疙瘩的疗效。此外，还使用培养的瘢痕疙瘩衍生成纤维细胞研究了潜在的分子机制。
4 名患者每 2 个月接受一次直接注射到瘢痕疙瘩中的 BTA（剂量从 70 到 140 Speywood 单位不等），最多持续 6 个月。通过临床评估和使用三维光学轮廓系统测量来评估高度和体积的差异。用不同浓度的 BTA 处理瘢痕疙瘩衍生的成纤维细胞，并通过实时定量 PCR 测定 COL1A1、COL1A2、COL3A1、TGF-β1、TGF-β2、TGF-β3、纤连蛋白-1、层粘连蛋白-β2 和α-SMA 的表达。MTT 和 BrdU 测定用于分析 BTA 对成纤维细胞增殖和代谢的影响。
BTA 的瘢痕内给药并未导致瘢痕组织消退。BTA 处理瘢痕疙瘩成纤维细胞后，ECM 标志物、胶原合成或 TGF-β 的表达没有差异。此外，BTA 处理对瘢痕疙瘩成纤维细胞的增殖和代谢没有影响。
本研究未能证实 BTA 对存在的瘢痕疙瘩的治疗作用的临床效果。基于我们的数据，BTA 对瘢痕疙瘩衍生成纤维细胞的潜在作用机制仍不清楚。
