分子对接分析地高辛生物选择性拮抗RORγt活性.PDFVIP

J South Med Univ, 2014, 34(4): 511-518 doi 10.3969/j.issn. 1673-4254.2014.04.16 ·511 · 基础研究 分子对接分析地高辛衍生物选择性拮抗分子对接分析地高辛衍生物选择性拮抗RORRORγγtt 活性活性 1 1 1 2 1 1 1 1 钟彩梅 ，蔡译萱 ，王美容 ，郑秀芬 ，邱贤文 ，孙乐栋 ，张 帆 ，张堂德 1 2 南方医科大学珠江医院皮肤病与性病科，广东 广州 510282；南方医科大学附属顺德第一人民医院皮肤科， 广东 顺德 528000 摘要：目的银屑病是一种慢性炎症性免疫性疾病，与Th 17细胞的功能失调密切相关。RORγt 影响Th 17细胞的分化、成熟；并 在该细胞所致的免疫紊乱中发挥极为重要的作用。本文主要探讨地高辛衍生物选择性拮抗RORγt 转录活性的潜在机制。方 法 地高辛为对照，通过分子对接的方法结合分子间的静电势能（MEP）分析地高辛衍生物（Dhd）与RORs （RORα，RORβ和 RORγt）的相互作用；通过荧光素酶报告基因系统进一步验证分子对接结果。结果 分子对接结果示Dhd 仅影响RORγt 分子构 象；荧光素酶报告基因检测示Dhd 选择性拮抗RORγt 转录活性，该拮抗作用可呈时-效性和量-效性。结论 Dhd 选择性拮抗 RORγt 转录活性。 关键词：RORγt ；分子对接；地高辛；免疫性疾病 Investigation of selective inhibition of digoxin derivative on retinoic acid-related orphan nuclear receptor γt transcription activity using molecular docking 1 1 1 2 1 1 1 1 ZHONG Caimei , CAI Yixuan , WANG Meirong , ZHENG Xiufen , QIU Xianwen , SUN Ledong , ZHANG Fan , ZHANG Tangde 1Department of Dermatology and Venereology, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China; 2Department of Dermatology, Shunde First Peoples Hospital Affiliated to Southern Medical University, Shunde 528000, China Abstract: Objetive Psoriasis is an autoimmune-related chronic inflammatory skin disease strongly associated with the dysfunction of Th17 cells. Retinoic acid-related orphan nuclear receptor γt (RORγt) plays a critical role in the differentiation and maturation of Th17 cells and in cell-derived immunologic derangement. We conducted this study to investigate potential mechanism by which the derivative of digoxin selectively antagonizes RORγt transcriptional activity. Method Using molecular docking in combination with molecular el