水飞蓟宾，一种黄酮木脂素类化合物，是临床常用的保肝药物。近年来发现它更多方面的药理学活性，如抗肿瘤、抗糖尿病和抗神经退化等。课题组前期体内外研究均发现水飞蓟宾具有抗皮肤UVB损伤的作用，且在表皮和真皮中存在机制上的明显差异。基于水飞蓟宾的结构，它被推测具有雌激素样作用。一些研究也证明了它的雌激素样作用，但极具复杂性，目前尚未研究清楚。雌激素受体主要包括ERα和β两种亚型，二者功能和分布上均有较大差异。ERs除了经典的入核调节基因转录这一作用外，现已发现均能在细胞膜和线粒体上发挥直接作用，但研究尚不充分。本课题将对细胞核、细胞膜和线粒体上的ERs分布以及功能进行考察，以获得ERs在水飞蓟宾抗表皮和真皮UVB损伤方面的作用。研究将在人永生化角质形成细胞HaCaT和人包皮成纤维HFF细胞中同时展开，并在小鼠表皮和真皮组织中验证。研究结果将充实水飞蓟宾的保护机制，同时完善ERs的三种信号通路。

The flavonolignan silibinin was a commonly used hepatoprotective drug. In recent years, many new pharmacological roles of this old compound were found, including the anti-tumor, anti-diabetes and anti-neuron degeneration effects. Our previous researches have also found that silibinin protected the skin against ultraviolet B (UVB) injury both in vitro and in vivo, and the underlying mechanisms in epidermal and dermal cells or tissues were totally different. Based on the chemical structure, silibinin was supposed to have estrogen-like effects. Indeed, some studies showed the estrogen-like action of silibinin, however, this action was too complex to be elucidated clearly. Estrogen receptors were typically classified to a subtype of estrogen receptor α and another type of β (ERα and β), which had large differences in both function and distribution in cells. Besides the classical regulation of gene transcription in the nucleus, ERs were also found to directly act on the cell membrane and mitochondria, which had not been fully discussed. This subject was designed to study the cellular distribution of ERs on different locations, particularly the cellular nucleus, cell membrane and mitochondria and their different biological activity, and aimed to get the roles of ERs in the protection of silibinin against UVB damage on epidermal and dermal cells. The study would be done on the human immortalized keratinocytes HaCaT cells and human foreskin fibroblasts HFF cells simultaneously, and verified on murine epidermis and dermis. The results are promised to enrich the protective mechanisms of silibinin and the three different signalling pathways of ERs.