银屑病是一种慢性炎症性疾病，需要长期规范治疗。弱效糖皮质激素是轻中度银屑病的常用外用制剂，但停药后反弹复发的机制仍未明了。最新研究提示细胞核内转录调控信号通路Akt/NF-κB的上游前炎症因子Cyr61可作为干预新靶点。课题组外用三草软膏预处理的银屑病动物模型显示炎症减轻，并伴有Cyr61mRNA表达降低，而糖皮质激素对Cyr61无影响。基于以上差异，课题组提出“糖皮质激素抑制下游炎症反应，但皮损中Cyr61仍持续高表达，这可能是糖皮质激素停药后银屑病复发的重要因素之一。预防性使用三草软膏，可降低前炎症因子Cyr61，改善Akt/NF-κB核转录激活，预防炎症复发”的科学假说。本项目拟运用CRISPR/Cas9基因敲除、质粒转染、单克隆抗体中和、活性荧光标记技术，阐释预防性外用三草软膏对银屑病炎症的抑制。本研究对丰富中医外治法的科学内涵，体现祖国医学“治乱安危”的整体思想具有积极意义。

Psoriasis is a chronic inflammatory disease that requires long-term standard treatment. The weak glucocorticoids are commonly used topical formulations to treat mild to moderate psoriasis, however the mechanism of relapse after discontinuation is still unknown. The latest study shows that upstream proinflammatory cytokine Cyr61 can be used as a new intervention target, which might be through the regulation ofAkt/NF-κB signaling pathway . The expression of Cyr61 was high in patients with psoriasis. In addition, the animal model of psoriasis treated with external application of Three Grass ointment showed that the inflammation was relieved and the expression of Cyr61 mRNA was decreased, but the glucocorticoid had no effect on Cyr61. Based on the above observations, we suggested a hypothesis that “glucocorticoids inhibit the downstream inflammatory responsebut has no effect on expression of Cyr61 , which may be one of the important factors for the recurrence of psoriasis after glucocorticoid withdrawal. Prophylactic use of Three Grass ointment can reduce proinflammatory cytokine Cyr61, improving the Akt/NF-κB nuclear transcription activation, preventing the recurrence of inflammation". The project intends to use CRISPR/Cas9 gene knockout plasmid, plasmid transfection, neutralizing monoclonal antibody, immunofluorescence technique to explain why prophylactic use of Three Grass ointment inhibits psoriasis inflammation. This study will enrich the scientific connotation of Chinese medicine external treatment, playing a positive role on holistic concept "manage chaos and appease danger" of traditional Chinese medicine.