银屑病严重危害患者身心健康。流行病学证实，银屑病与代谢综合征（MS）关系密切，合并MS病情重、疗效差、易复发，但MS加重银屑病的机制尚不十分清楚。研究表明，MS诸多炎症因子，如IL1β、Leptin、IL17等可诱导多种细胞胰岛素抵抗，并进一步加重机体炎症反应。我们前期研究发现，银屑病合并MS时表皮角质形成细胞（KC）存在显著的胰岛素抵抗，TNFα等炎症因子产生增加，给予胰岛素增敏剂可减少炎症因子，明显增进疗效。这些结果强烈提示KC胰岛素抵抗在MS加重银屑病中发挥重要作用。本项目拟从临床标本、细胞水平和动物实验三个方面，进一步明确KC胰岛素抵抗在银屑病中的作用，探讨MS诱导KC胰岛素抵抗的机制，全面阐明MS诱导KC胰岛素抵抗加重银屑病恶性循环的分子网络。预期结果有助于深入认识KC胰岛素抵抗在MS加重银屑病中的作用及机制，并为改善伴有MS的银屑病顽固、易复发等治疗难点提供新的治疗策略和靶点。

Psoriasis is a common, chronic inflammatory skin disorder, which can significantly impact quality of life. The prevalence of metabolic syndrome (MS) in patients with psoriasis ranges from 20% to 50%. The strength of these associations has been repeatedly confirmed by increasing observational studies. MS is more common in patients with severe psoriasis than in those with mild psoriasis and associates with longer psoriatic treatment and shorter length of remission. These results, suggest that MS can affect the severity and the treatment response of psoriasis, the mechanism of which has not been understood. .MS is a state of chronic low-grade inflammation established by the production of various pro-inflammatory cytokines, such as IL1β, leptin and IL17. These cytokines can induce insulin resistance of many kinds of cells. It is well-established that insulin resistance and inflammation form a vicious circle, with each condition promoting the other and accelerating the development of metabolic disorders..Our previous results have found that there exists intense insulin resistance in epidermis in psoriatic patients with MS and metformin can ameliorate the resistance of MS to psoriatic therapy, which suggests that insulin resistance of KC exerts important role in MS worsening psoriasis. .This project intends to take psoriasis with metabolic syndrome as the research object and to perform research from the view of clinical specimens, cell and animal model aspects respectively to explore the role of insulin resistance of KC in the aggravation of psoriasis induced by MS, illuminating the molecular mechanism of the relationship between MS and psoriasis. The anticipated results will contribute to better understand the function and action mechanism of KC insulin resistance, and help to understand the molecular regulation of KC insulin resistance between MS and psoriasis, and will also provide new strategy and target for the treatment of psoriatic patients with MS.