ROS/TSPO诱导的炎性反应在白癜风发病中的作用及分子机制研究

应激状态下，黑色素细胞产生和释放损伤相关模式分子（ROS、炎症因子）是造成白癜风发病的重要因素。到目前为止，有关黑色素细胞中ROS、炎症因子产生的机理尚未完全阐明。课题组前期研究发现，白癜风病变周围组织中线粒体转位蛋白18kDa（TSPO）表达量异常升高。在白癜风豚鼠模型中，TSPO配体Ro5-4864可以抑制过氧化氢所致的黑色素细胞破坏。最新研究表明，TSPO在应激状态下高表达，参与ROS生成及炎性反应，是一个备受关注的治疗靶点。因此，我们提出新假说：TSPO促进黑色素细胞中ROS、炎症因子的产生及释放，进而参与白癜风的发生发展。基于此，本项目拟构建TSPO基因沉默/过表达的黑色素细胞模型、黑色素细胞特异性的条件性Tspo基因敲除小鼠模型，深入研究TSPO在促进ROS、炎症因子产生及释放中的分子机制，明确TSPO在白癜风发病中的作用。为白癜风的预防和治疗提供新的靶点。

The production and release of damage-associated molecular patterns (ROS, inflammatory factors) by melanocytes play an important role in vitiligo pathogenesis. So far, the formation mechanism of ROS and inflammatory factors in melanocytes has not been fully elucidated. Our previous studies suggested that the expression of translocation protein 18 kDa (TSPO) was abnormally increased in vitiligo perilesional skin. In the vitiligo guinea pig model, TSPO ligand Ro5-4864 inhibited the destruction of melanocytes caused by hydrogen peroxide. Therefore, we propose a hypothesis: TSPO promotes the production and release of ROS and inflammatory factors in melanocytes, and then participates in the occurrence and development of vitiligo. Based on this, this project intends to build Tspo gene silencing or overexpression melanocyte model, melanocyte-specific conditional Tspo gene knockout mice model, and study the molecular mechanism of TSPO in promoting ROS and inflammatory factors production. This study aims to clarify the role of TSPO in the pathogenesis of vitiligo and provide a new target for the prevention and treatment of vitiligo.