小柴胡汤经cAMP/PKA信号通路影响皮肤黑素合成的机制研究

The study plans to select B16 mouse melanoma cells as the research object to simulate the environment of melanin metabolism obstacles inside the body. It would study the possible signal pathway and key regulation point in Xiaochaihu Decoction’s inhibition of melanogenesis from the level of gene and protein on the basis of previous studies which have certified that Xiaochaihu Decoction can inhibit melanogenesis, and illuminate that the Decoction affects the possible molecular mechanism mainly by inhibiting the cAMP/PKA signal pathway, decreasing the expression of MITF to reduce melanogenesis, in the hope that the classical prescriptions could be employed in modern ways so as to expand the scope of clinical application, and provide experimental foundation for the research of a kind of safe and efficient skin depigment agent which affects melanogenesis from multiple target points and multiple links applied in the clinic treatment of skin pigmentary disorder. Meanwhile, take PDE4D3 as possible key function target point, and figure out whether the regulation of cAMP/PKA/MITF by Xiaochaihu Decoction relies on the participation of PDE4D3, so as to provide experimental foundation for the research of skin depigment agent with optional function on PDE4D3, and theoretical foundation for the experiment of taking PDE4D3 as target point to regulate MITF gene expression and control skin pigmentation as well.

目前国内外的研究者都在不遗余力的寻找安全、高效的皮肤美白剂以对抗皮肤色素沉着问题。小柴胡汤为著名的和解少阳剂，既往研究我们已证实其可通过抗氧化、抑制酪氨酸酶活性而抑制黑素合成，本次研究拟选择B16鼠黑素瘤细胞为研究对象，从基因、蛋白等水平研究参与小柴胡汤抑制黑素合成可能的信号通路和关键调控点，阐明其作用的分子机制主要通过抑制cAMP/PKA信号通路，下调MITF表达而减少黑素合成，以期古方新用扩大小柴胡汤的临床应用范围，为研发一种从多靶点多环节影响黑素合成，安全高效的皮肤美白剂提供实验依据。同时将PDE4D3作为可能的关键作用靶点，研究小柴胡汤对cAMP/PKA/MITF通路的调节是否依赖于PDE4D3的参与，为研发选择性作用于PDE4D3的皮肤美白剂奠定实验基础，并为将PDE4D3作为靶点调节MITF基因表达和控制皮肤色素沉着提供理论依据。