雷铁池 皮肤增白剂研究进展与思考.pptVIP

Thank you for your attention! 雷铁池 武汉大学人民医院皮肤科 皮肤增白剂的研究进展与思考 Skin complexion 表皮黑素细胞合成黑素（melanin）的质和量是决定人皮肤颜色（complexion）主要因素。健康的皮肤着色（pigmentation）除了能赋予皮肤强大的光保护能力和渗透性屏障等生理功能外，还能给人增添社交自信与魅力 Undesired hyperpigmentation 除去病理性皮肤色素增加如黄褐斑、炎症后色素沉着斑等，改善皮肤不理想的肤质是人类一直在追求的梦想 目前，皮肤增白剂（美白剂）市场庞大且混乱，缺乏疗效评定的金标准 Epidermal Melanin Unit 位于表皮基底层的黑素细胞合成特有的黑素小体，并转移至邻近的角质形成细胞，构筑成皮肤的基础着色(constitutive pigmentation) 50 ?m Melansomes in recipient KCs Melanosomes in recipient KCs of the basal and/ suprabasal layer are dispersed randomly, also quickly aggregated to form “supranuclear cap-like structure (A) upon exposure to UVR. Eventually move upward to horny layer to be broken up (B). A B Melanins and melanosomes 整个黑素生成的生化途径被严格限定于一个膜性细胞器黑素小体内（melanosome） 黑素生成所需的酶蛋白（tyrosinase, Tyrp1, and Dct)和结构蛋白（Pmel17/gp100）通过各自的cargo蛋白被运输至前黑素小体囊泡 成熟黑素小体被认为地分为：I-IV期 Nucleus Golgi SER Premelanosome RER IV melanosome III melanosome II melanosome I melanosome Coated Vesicle The biogenesis of melanosome Pathway of eumelanin synthesis 表皮黑素细胞黑素合成的生化途径及相关基因调节 L-酪氨酸 L-多巴 L-多巴醌 多巴色素 5,6-二羟基吲哚(DHI) 5,6-二羟基吲哚羧酸(DHICA) CO2 多巴色素异构酶(Dct/Tyrp2) 5,6-吲哚醌 5,6-吲哚醌羧酸 DHI-优黑素 DHICA-优黑素 酪氨酸酶 酪氨酸酶相关蛋白-1(Tyrp1) 酪氨酸酶 Tyrosine DOPA DOPA-quinone DOPA-chrome DHICA DHICA-melanin DHI DHI-melanin Pheo-melanin Tyrosinase Dct / TRP2 TRP1 Schematic of the melanin biosynthetic pathway Visualization of purified melanosomes from MNT1 melanoma cells by TEM and SEM 2 ?m 2 ?m Stage III IV melanosomes were purified from cultured MNT1 cells by a sucrose gradient protocol Detailed structure of Eu-melanin particles observed by atomic force microscopy (AFM) Fine images of a typical Sepia (墨鱼) eumelanin aggregate deposited on mica from stock eumelanin solution. Smaller eumelanin particles are observed surrounding the micron-sized aggregate, and filaments are seen on much of the surface Clancy CMR, Simon JD. Biochemistry, 2001, 40:13353-60 Strategies of skin whitening agents 皮肤脱色（增白）剂可能的机制与作用靶点 酪氨酸酶抑制型 抑制tyr mRNA转录：H2O2、ASP、神经酰胺等 干扰tyr糖基化：谷胱甘肽、铁蛋白、氨