从SCCA2调控未折叠蛋白反应探讨凉血潜阳法对银屑病的作用机制

Based on the clinical efficacy of "cooling blood and latent yang" in the treatment of psoriasis, cooling blood and Qianyang method can down-regulate the expression of squamous cell carcinoma antigen 2 (SCCA2) in psoriasis patients and psoriasis-like mice. Combined with SCCA2 aggravatd the inflammation by activating unfolded protein reaction (UPR). The hypothesis is put forward that "The key link of cold blood and latent Yang therapy on psoriasis is closely related to the regulation of UPR by SCCA2. Taking IMQ-induced mouse psoriasis-like model and human immortalized keratinocytes (HaCaT) as the research objects, through lentivirus system silencing or overexpression of SCCA2 gene, combined with Real-Time PCR, Western blot, immunohistochemistry and other experimental techniques, clarify the mechanism of SCCA2 activating UPR to aggravate inflammatory response in psoriasis and explore how the method of cooling blood and latent Yang can inhibit inflammation through regulating UPR by SCCA2.

基于“凉血潜阳法”治疗银屑病的临床疗效，在明确凉血潜阳法下调银屑病患者和小鼠银屑病样皮炎中鳞状细胞癌抗原2（SCCA2）表达，结合SCCA2通过激活未折叠蛋白反应（UPR）促进炎症，申请人提出“凉血潜阳法作用于银屑病的关键环节与SCCA2调控UPR密切相关”假说。项目以IMQ诱导的小鼠银屑病样模型和人永生化角质形成细胞（HaCaT）为研究对象，通过慢病毒系统沉默或过表达SCCA2基因，结合Real-Time PCR、Western blot、免疫组化等实验技术，明确SCCA2激活UPR加重银屑病炎症反应的作用机制，探讨凉血潜阳法如何通过SCCA2调控UPR抑制炎症反应。

基于“凉血潜阳法”对银屑病患者的临床疗效，进一步发现：凉血潜阳法可以下调银屑病患者和小鼠银屑病样皮炎中鳞状细胞癌抗原2（SCCA2）的表达，为明确在银屑病中凉血潜阳中药和SCCA2的关系，以IMQ诱导的小鼠银屑病样模型和M5诱导的银屑病样细胞模型为研究对象，通过SCCA2基因敲除小鼠，慢病毒系统构建的SCCA2沉默或过表达的HaCaT细胞，结合Real-Time PCR、Western blot、免疫组化等实验技术进行一系列系统研究，实验结果表明：1）Serpinb3a（SCCA2 小鼠的同系物）促进银屑病样炎症在IMQ诱导的银屑病样小鼠; 2）SCCA2促进角质形成细胞炎症在M5诱导的银屑病样细胞模型；3）SCCA2激活p38MAPK信号通路在银屑病样小鼠和银屑病样细胞模型中；4）凉血潜阳中药通过抑制SCCA2下调p38MAPK通路改善角质形成细胞炎症，为凉血潜阳中药治疗银屑病提供了科学的实验数据。