PDF(Pubmed)
Abstract：
BACKGROUND: Although reports suggest that tranexamic acid (TXA) has clinical benefits for melasma patients by oral, intralesional and topical treatment, the optimal route of TXA therapy and the underlying mechanism involved remain poorly defined.
OBJECTIVE: To compare the skin lightening effect between oral TXA and topical TXA and to dissect the molecular mechanisms using ultraviolet B (UVB)-induced hyperpigmentation mouse model, ex vivo cultured human skin explant, and cultured melanocytes (MCs) and endothelial cells.
METHODS: Melanin content and cluster of differentiation 31 (CD31)-positive cell numbers were measured in tail skins from UVB-irradiated mice treated by intragastral or topical TXA using immunofluorescent and Fontana-Masson staining. The conditioned medium (CM) was harvested from human umbilical vein endothelial cells treated with or without 3 mM TXA and was used to treat MCs for 48 hours. mRNA and protein levels of tyrosinase and microphthalmia-associated transcription factor were measured using quantitative real-time reverse transcription polymerase chain reaction and western blotting assays. HMB45- and CD31-positive cell numbers as well as melanin content were also examined in ex vivo cultured human skin explants.
RESULTS: The hyperpigmented phenotype were significantly mitigated in UVB-irradiated tail skin plus intragastral TXA-treated mice compared with mice treated with UVB only or with UVB plus topical TXA. CD31-positive cell numbers correlated with the anti-melanogenic activity of TXA therapy. The data from cultured cells and skin tissues showed that suppression of endothelin-1 (ET-1) in vascular endothelial cells by TXA reduced melanogenesis and MC proliferation.
CONCLUSIONS: Oral TXA outperforms topical TXA treatment in skin lightening, which contributes to suppression of ET-1 in dermal microvascular endothelial cells by TXA.
OBJECTIVE: To compare the skin lightening effect between oral TXA and topical TXA and to dissect the molecular mechanisms using ultraviolet B (UVB)-induced hyperpigmentation mouse model, ex vivo cultured human skin explant, and cultured melanocytes (MCs) and endothelial cells.
METHODS: Melanin content and cluster of differentiation 31 (CD31)-positive cell numbers were measured in tail skins from UVB-irradiated mice treated by intragastral or topical TXA using immunofluorescent and Fontana-Masson staining. The conditioned medium (CM) was harvested from human umbilical vein endothelial cells treated with or without 3 mM TXA and was used to treat MCs for 48 hours. mRNA and protein levels of tyrosinase and microphthalmia-associated transcription factor were measured using quantitative real-time reverse transcription polymerase chain reaction and western blotting assays. HMB45- and CD31-positive cell numbers as well as melanin content were also examined in ex vivo cultured human skin explants.
RESULTS: The hyperpigmented phenotype were significantly mitigated in UVB-irradiated tail skin plus intragastral TXA-treated mice compared with mice treated with UVB only or with UVB plus topical TXA. CD31-positive cell numbers correlated with the anti-melanogenic activity of TXA therapy. The data from cultured cells and skin tissues showed that suppression of endothelin-1 (ET-1) in vascular endothelial cells by TXA reduced melanogenesis and MC proliferation.
CONCLUSIONS: Oral TXA outperforms topical TXA treatment in skin lightening, which contributes to suppression of ET-1 in dermal microvascular endothelial cells by TXA.
摘要：
背景：尽管有报道表明氨甲环酸（TXA）通过口服对黄褐斑患者具有临床益处，病灶内和局部治疗，TXA治疗的最佳途径和相关机制仍不明确.
目的：比较口服TXA和外用TXA的美白效果，并利用紫外线B（UVB）诱导的色素沉着过度小鼠模型剖析其分子机制，离体培养的人皮肤外植体，和培养的黑素细胞（MC）和内皮细胞。
方法：使用免疫荧光和Fontana-Masson染色，在经腹内或局部TXA处理的UVB照射小鼠的尾部皮肤中测量黑色素含量和分化簇31（CD31）阳性细胞数。条件培养基(CM)从用或不用3mMTXA处理的人脐静脉内皮细胞收获,并用于处理MC48小时。使用定量实时逆转录聚合酶链反应和蛋白质印迹测定法测量酪氨酸酶和小眼症相关转录因子的mRNA和蛋白质水平。还在离体培养的人皮肤外植体中检查了HMB45和CD31阳性细胞数以及黑色素含量。
结果：与仅用UVB或UVB加局部TXA治疗的小鼠相比，在UVB照射的尾部皮肤加胃胃内TXA治疗的小鼠中，色素沉着表型明显减轻。CD31阳性细胞数与TXA治疗的抗黑色素生成活性相关。来自培养细胞和皮肤组织的数据表明，TXA抑制血管内皮细胞中的内皮素-1（ET-1）可减少黑素生成和MC增殖。
结论：口服TXA在皮肤美白方面优于局部TXA治疗，这有助于TXA抑制真皮微血管内皮细胞中的ET-1。
目的：比较口服TXA和外用TXA的美白效果，并利用紫外线B（UVB）诱导的色素沉着过度小鼠模型剖析其分子机制，离体培养的人皮肤外植体，和培养的黑素细胞（MC）和内皮细胞。
方法：使用免疫荧光和Fontana-Masson染色，在经腹内或局部TXA处理的UVB照射小鼠的尾部皮肤中测量黑色素含量和分化簇31（CD31）阳性细胞数。条件培养基(CM)从用或不用3mMTXA处理的人脐静脉内皮细胞收获,并用于处理MC48小时。使用定量实时逆转录聚合酶链反应和蛋白质印迹测定法测量酪氨酸酶和小眼症相关转录因子的mRNA和蛋白质水平。还在离体培养的人皮肤外植体中检查了HMB45和CD31阳性细胞数以及黑色素含量。
结果：与仅用UVB或UVB加局部TXA治疗的小鼠相比，在UVB照射的尾部皮肤加胃胃内TXA治疗的小鼠中，色素沉着表型明显减轻。CD31阳性细胞数与TXA治疗的抗黑色素生成活性相关。来自培养细胞和皮肤组织的数据表明，TXA抑制血管内皮细胞中的内皮素-1（ET-1）可减少黑素生成和MC增殖。
结论：口服TXA在皮肤美白方面优于局部TXA治疗，这有助于TXA抑制真皮微血管内皮细胞中的ET-1。
