白杨素对急性痛风性关节炎NLRP3炎性体的作用机制探讨  

The mechanism of the effect of chrysin on the inflammatory body of NLRP3 in acute gouty arthritis

作　　者：张涵[1] 丁雨琦 陈伟圣 金丽霞[1] 金怡[1] Zhang Han

机构地区：[1]浙江中医药大学,310053 [2]浙江中医药大学滨江学院,310053

出　　处：《浙江临床医学》2020年第1期14-16,共3页Zhejiang Clinical Medical Journal

基　　金：浙江省公益性技术应用研究计划(2017C33107)。

摘　　要：目的探讨白杨素对小鼠急性痛风性关节炎(AGA)NLRP3炎性体的作用机制.方法收集与NLRP3炎性体有关的通路蛋白作为受体,白杨素为配体,Discovery Studio 2.5预处理后利用软件Auto Dock进行分子模拟对接,以结合能(Binding?Energy)和抑制常数(Inhibt Constant)作为评分标准筛选出对接较好的靶点蛋白进行分析,推测其作用机制和靶点;注射尿酸钠于小鼠足掌建立AGA模型,验证分子对接结果,进一步推测白杨素抗急性痛风性关节炎的作用靶点和机制.结果分子对接数据提示白杨素可作用于NLRP3炎症信号通路起到治疗效果,其中白杨素可与NLRP3炎性体轴中多个蛋白结合,其中又以NLRP3和半胱天冬酶-1(caspase-1)蛋白对接较好;动物实验证明白杨素可降低NLRP3炎性体中的NLRP3和caspase-1蛋白表达,缓解AGA,又能降低脏器指数,改善体征.结论白杨素可作用于NLRP3炎性体中的NLRP3和caspase-1蛋白,抑制NLRP3炎性体活性,从而防治AGA.Objective To explore the mechanism of chrysin in the treatment of gouty arthritis based on NLRP3 inflammasomes signaling pathway by molecular docking technique and animal experiment.Methods The pathogen proteins related to NLRP3 inflammasomes were collected as a receptor and were pretreated with Discovery Studio 2.5 as a receptor,while chrysin were used as a ligand.The ligand-receptor molecular docking was calculated by Auto Dock,and the point proteins were analyzed according to the Binding Energy and Inhib Constant to find better docking targets.The acute gouty arthritis model was established by injecting MSU into the paw of mice,and the molecular docking results were verified,further speculate on the target and mechanism of chrysin against acute gouty arthritis.Results Molecular docking data suggested that chrysin could act on NLRP3 inflammatory signaling pathway,and the bindings of chrysin to NLRP3 and caspase-1 protein were better.Animal experiments showed that chrysin could decrease NLRP3,caspase-1 protein expression in NLRP3 inflammasome and reduce organ index to relieve acute gouty arthritis and protect the kidney.Conclusion Chrysin can act on proteins like NLRP3 and caspase-1 from NLRP3 inflammasome to against gouty arthritis.

关 键 词：白杨素 急性痛风性关节炎 分子对接 机制 NLRP3炎性体 

分 类 号：R28[医药卫生—中药学]