中文摘要
银屑病是一种常见的慢性皮肤病,其发生发展与遗传和环境因素相关。目前其治疗的热点是生物制剂和免疫靶向治疗,其中IL-12/23 p40 单克隆抗体(商品名:Ustekinumab,优特克单抗)以其治疗的高显效率和缓解的长期性脱颖而出。它是全人源化的IgG1κ单克隆抗体,通过与IL-12和IL-23的共同亚单位p40结合,有效抑制二者活性,阻止免疫细胞活化,达到治疗目的。既往的研究已明确p40单抗在银屑病的治疗中通过激活外周血单个核细胞来调节细胞因子,但是尚无p40单抗如何通过外周血单个核细胞而影响人角质形成细胞的细胞学行为及其涉及的细胞通路的研究。本课题拟通过离体和体外研究,以接受p40 单抗治疗前后的银屑病患者的血液和皮肤样本为研究对象,通过芯片技术,细胞功能及相关信号通路的检测,探讨p40单抗治疗银屑病的系统机制,为其药物研发开辟新思路。
英文摘要
Psoriasis is a common chronic skin disease, whose development depends on genetic factor and immune environment. Biologics is popular in psoriasis treatment for its immune-targeted. IL-12/23 p40 monoclonal antibody (ustekinumab) is effective and long-lasting, which is a fully human IgG1κ monoclonal antibody that inhibits IL-12 and IL-23 activity by binding to the p40 subunit of IL-12 and IL-23, prevents immune-cell activation and shows therapeutic effects. The previous studies have proven that p40 monoclonal antibody regulates cytokine secretion by activating PBMC (peripheral blood mononuclear cell), however, the study on how to affect keratinocyte by activating PBMC and the involved cell signals was lacked. Our group planned to study the systemic mechanism of ustekinumab in the treatment of psoriasis with blood and skin biopsy samples of psoriatic patients which received ustekinumab treatment, from which we may develop a new way to psoriasis treatment.
结题摘要
银屑病是一种常见的慢性皮肤病,其发生发展与遗传和环境因素相关。目前其治疗的热点是生物制剂和免疫靶向治疗,其中IL-12/23 p40 单克隆抗体(商品名:Ustekinumab,优特克单抗)以其治疗的高显效率和缓解的长期性脱颖而出。它是全人源化的IgG1κ单克隆抗体,通过与IL-12和IL-23的共同亚单位p40结合,有效抑制二者活性,阻止免疫细胞活化,达到治疗目的。既往的研究已明确p40单抗在银屑病的治疗中通过激活外周血单个核细胞来调节细胞因子,但是尚无p40单抗如何通过外周血单个核细胞而影响血液中的细胞因子表达及其涉及的细胞通路的研究。本课题拟通过离体研究,以接受p40 单抗治疗前后的银屑病患者的血液样本为研究对象,通过检测血清表达和外周血单个核细胞的mRNA水平,及相关信号通路的探索,探讨p40单抗治疗银屑病的系统机制,为其药物研发开辟新思路。
