中文摘要
银屑病发病基础与皮肤屏障功能受损密切相关,表皮细胞间的紧密连接被认为是表皮屏障功能的“主要控制因子”。银屑病皮损区紧密连接的破坏与慢性炎症相互促进,形成恶性循环,维持皮损区的炎症反应。表皮屏障的修复是临床治疗的重要手段之一。血燥证是银屑病慢性病程的主要证候,病机为阴血津液亏虚、兼有毒邪,临床以养血滋阴、润燥解毒为法,养血解毒方有良好的临床疗效。前期研究证实该方明显改善表皮屏障功能,并具有恢复紧密连接蛋白(claudin-1)表达的作用。以此为线索,本项目通过临床皮损检测及动物实验,进一步明确养血解毒方对紧密连接功能、蛋白表达及定位的调节作用,并探索养血解毒方的作用环节。同时通过炎性因子刺激的表皮细胞体外模型结合表达谱芯片检测,观察养血解毒方对“差异基因→紧密连接调节通路”的干预作用,阐明养血解毒方的作用靶点。通过临床、动物、细胞多层次的研究,为养血解毒方治疗银屑病的临床应用提供生物学证据。
英文摘要
Tight junction between epithelial cells is a major controlling factor of skin barrier, whose dysfunction contributes to the process of psoriasis. The disrupted tight junction promotes chronic inflammatory response, which in turn amplifies the damage in psoriatic involved skin. Damage repair of epithelial barrier is one of the most effective treatments for psoriasis. The blood-dryness is the main syndrome of chronic course of patients with psoriasis. The pathogenesis of blood-dryness formed by blood deficiency caused by Yin loss with poison heat hurting. In clinical, nourishing blood and detoxification is the principle and Yang xue huo xue jie du prescription is an effective prescription. Our previous research demonstrated that decoction markedly improved the skin barrier function via strengthening claudin-1 protein expression. Along this line, we try to better our understanding of decoction via investigating the regulatory effect of decoction on the function of tight junction, as well as relative proteins expression and location in clinical psoriatic involved skin samples and animal experiments. Moreover, we employ in vitro epithelial cells model treated by inflammatory cytokines to perform gene expression microarrays, attempting to reveal the intervention effect and mechanisms of decoction on differential gene-mediated signaling pathways. Via clinical detection, animal experiments in vivo and epithelial cells research in vitro, we try to uncover the mechanisms of decoction on treating psoriasis and provide the theoretical basis for clinical application.
