甲异靛通过TLR4-TAK-NF-κB途径治疗银屑病的机制研究  

Mechanism about therapeutic effect of meisoindigo on psoriasis via down-regulation of the TLR4-TAK-NF-κB pathways

作　　者：张海婧 张翼 金晶 周琬琪 陈晓光 

机构地区：[1]中国医学科学院北京协和医学院药物研究所天然药物活性物质与功能国家重点实验室,北京100050

出　　处：《药学学报》2013年第4期503-507,共5页Acta Pharmaceutica Sinica

基　　金：国家自然科学青年科学基金资助项目(81001443);医科院药物所基本科研业务费(2010CHX14)

摘　　要：在近年来的临床实践中发现,甲异靛对银屑病有很好的疗效,但作用机制不明。利用脂多糖刺激RAW264.7细胞后,发现甲异靛对其产生一氧化氮有明显的抑制作用。同时检测了甲异靛作用HaCaT细胞后对免疫相关细胞因子及上游通路细胞蛋白的影响。结果发现,甲异靛抑制了众多炎症相关因子的表达,如一氧化氮合成酶、环氧合酶2、肿瘤坏死因子等。对上游通路蛋白表达进行检测后发现,甲异靛可以相继抑制NF-κB、TAK和TLR4等蛋白的表达。本研究结果显示,甲异靛可以通过作用于TLR4-TAK-NF-κB通路,从而治疗或缓解银屑病。Meisoindigo is an indigo natural derivative commonly used in anti-cancer therapy. In the clinical application, it was also found to have good therapeutic effect on psoriasis. In order to further understand its mechanism of action, human normal keratinocyte cell line HaCaT and RAW 264.7 were used to identify if meisoindigo could affect the inflammatory factors such as NO and other important cytokines which were highly involved in psoriasis. Our results indicated that meisoindigo decreased the production of NO in LPS-stimulated RAW 264.7 cells and reduced the expression of cytokines in LPS-stimulated HaCaT cells. And TLR4-TAK-NF-xB was a possible pathway mainly involved in the attenuation of iNOS and pro-inflammatory cytokine production by meisoindigo, which may take part in the therapeutic effect of meisoindigo on psoriasis.

关 键 词：甲异靛 银屑病 细胞因子 

分 类 号：R963[医药卫生—微生物与生化药学]