From the Department of Plastic and Reconstructive Surgery, Korea University Medical Center.
Plast Reconstr Surg. 2019 Aug;144(2):347-356. doi: 10.1097/PRS.0000000000005838.
Hyperpigmentation following ultraviolet irradiation has cosmetic concerns. Botulinum toxin type A can favorably affect skin pigmentation. However, the mechanism of skin pigmentation is unclear.
In vitro, human epidermal melanocytes were co-cultured with human keratinocytes. After cells were treated with botulinum toxin type A, cell morphology, proliferation, and dendricity were analyzed, and immunofluorescence, tyrosinase activity, and melanin contents were determined. To evaluate the effect of botulinum toxin type A on ultraviolet B-irradiated mouse skin, ultraviolet B alone was applied to one side of the back of each mouse as a control, whereas ultraviolet B plus injection of botulinum toxin type A was applied to the contralateral side. Skin pigmentation, histology, and the number of dihydroxyphenylalanine-positive melanocytes were evaluated. The L* colorimeter value was measured. Enzyme-linked immunosorbent assay determinations of basic fibroblast growth factor, interleukin-1 alpha, and prostaglandin E2 were performed.
Immunohistochemical staining revealed botulinum toxin type A in the cytoplasm of melanocytes and in the positive control. In vitro, melanocyte dendricity and melanin contents were decreased slightly but significantly (p < 0.05) after botulinum toxin type A treatment. In vivo, botulinum toxin type A suppressed skin pigmentation. The number of dihydroxyphenylalanine-positive melanocytes was also significantly lower than in the control side. Tyrosinase activity and melanin content were also significantly reduced (p < 0.05). Botulinum toxin type A also significantly reduced the amounts of basic fibroblast growth factor, interleukin-1 alpha, and prostaglandin E2 (all p < 0.05).
Botulinum toxin type A can suppress epidermal melanogenesis through both direct and indirect mechanisms.
紫外线照射后皮肤色素沉着会影响美观。肉毒毒素 A 可改善皮肤色素沉着，但皮肤色素沉着的机制尚不清楚。
在体外，将人类表皮黑素细胞与人类角质形成细胞共培养。用肉毒毒素 A 处理细胞后，分析细胞形态、增殖和树突状，并用免疫荧光、酪氨酸酶活性和黑色素含量进行测定。为评估肉毒毒素 A 对紫外线 B 照射小鼠皮肤的影响，一侧小鼠背部单独应用紫外线 B 作为对照，而对侧则同时应用紫外线 B 和肉毒毒素 A。评估皮肤色素沉着、组织学和二羟苯丙氨酸阳性黑素细胞数量。采用 L*比色计测量值。进行酶联免疫吸附测定以检测碱性成纤维细胞生长因子、白细胞介素-1α和前列腺素 E2。
免疫组化染色显示黑素细胞和阳性对照的细胞质中有肉毒毒素 A。体外实验中，肉毒毒素 A 处理后黑素细胞树突状和黑色素含量略有但显著减少（p<0.05）。体内实验中，肉毒毒素 A 抑制皮肤色素沉着。二羟苯丙氨酸阳性黑素细胞数量也明显低于对照组（p<0.05）。酪氨酸酶活性和黑色素含量也明显降低（p<0.05）。肉毒毒素 A 还显著降低碱性成纤维细胞生长因子、白细胞介素-1α和前列腺素 E2 的含量（均 p<0.05）。
肉毒毒素 A 可通过直接和间接机制抑制表皮黑色素生成。
