白癜风是一种危害人类健康的皮肤疾病，由于其发病机理和治疗靶点不明确，尚未开发出疗效显著的药物。大量临床观察及基础研究表明白癜风的发生发展与精神因素密切相关，是一种典型的身心疾患。我们课题组前期研究显示抗抑郁药氟西汀可改善精神应激导致的色素脱失损伤，且这一过程可能由5-HT1A进行介导；同时也发现5-HT1A/1B受体有可能成为精神性色素脱失疾病的潜在靶点。基于此，本项目以小鼠和斑马鱼为研究对象，通过建立应激色素脱失模型和经典白癜风模型，系统性地探讨氟西汀抗精神性白癜风效应的特异性和潜在作用靶点。利用连接生物素的氟西汀探针分子合成、基因突变质粒载体构建、斑马鱼基因敲除、siRNA介导的基因沉默等方法研究氟西汀抗白癜风的作用靶点及作用机制，从而为未来白癜风新药研发奠定一定的理论和技术基础，同时也为精神神经障碍导致皮肤疑难杂症的治疗提出新的思路和方向。

Vitiligo is such a harmful skin disease with unclear pathogenesis and therapeutic targets that effective drugs have not been developed yet. Clinical observation and experimental studies have shown that the development and progression of vitiligo are closely related to psychiatric factors. Thus, Vitiligo is a kind of typical physical and mental disorders. According to the previous studies of our research group, antidepressants fluoxetine could ameliorate stress-induced depigmentation probably mediated by 5-HT1A receptor. Besides, the 5-HT1A/1B receptor may be a potential target of psychiatric depigmentation diseases. Therefore, our research project is to systematically detect the specific effect and potential target of fluoxetine on mental vitiligo through the establishment of stress-induced depigmentation model and classic vitiligo model in mice and zebrafish. We will study the mechanism and targets of fluoxetine in the treatment of vitiligo using the methods of fluoxetine probe synthesis, gene mutation plasmid vectors building, 5-HT1A/1B gene knock-out in zebrafish and siRNA mediated gene silencing etc.. Then it will lay a strong theoretic and technical foundation for new anti-vitiligo drug research and development, as well as propose new ideas and directions in the treatment of psychotic disorders-associated dermatologic diseases.