类风湿性关节炎热证“药-证对应”机制的网络药理学研究  

The Molecular Mechanism of 'Herbs-Pattern Correspondence' in RA with Heat Pattern Based on Network Pharmacology

作　　者：牛旭艳[1] 李健[2] 吕诚[1] 李立[1] 郭洪涛[1] 刘春芳[3] 林娜[3] 吕爱平[1,4] 

机构地区：[1]中国中医科学院中医临床基础医学研究所,北京100700 [2]北京中医药大学基础医学院,北京100029 [3]中国中医科学院中药研究所,北京100700 [4]香港浸会大学中医药学院

出　　处：《中国实验方剂学杂志》2012年第8期299-303,共5页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：国家自然科学基金项目(81173628;30825047;90709007);科技部重大新药创制项目(2009zx09502-019;2009ZX09301-005)

摘　　要：以热证类风湿性关节炎(RA)为切入点,通过构建、分析其对应的分子网络及药物靶标网络,初步探讨"药-证对应"的机制。综合运用定向文本挖掘、PubChem小分子化合物数据库检索、临床典型热证RA患者外周血CD4+T细胞基因组学检测以及Ingenuity Pathway Analysis(IPA)网络构建等研究方法。通过定向文本挖掘,筛选出治疗RA热证的常用中药:黄柏、知母、苍术及牛膝4味中药。通过检索PubChem数据库,找到RA热证的对证中药共有靶蛋白123个。通过基因芯片技术,得到RA热证与正常人比较的差异基因21个。通过IPA软件分别构建RA热证和对证中药靶蛋白的分子相互作用网络。两个网络共有4条相同的生物学通路:GM-CSF(粒细胞巨噬细胞刺激因子)信号通路,CTLA4(细胞毒性T淋巴细胞相关抗原4)信号通路,T细胞受体信号通路及辅助T细胞中的CD28信号通路。这些细胞免疫反应相关的生物学通路,共同干预了细胞存活、细胞免疫及炎症反应等细胞生命活动。结果表明:RA热证的分子网络和对证中药靶点的分子网络所涉及的共同的生物学通路:GM-CSF信号通路,CTLA4信号通路,T细胞受体信号通路及辅助T细胞中的CD28信号通路可能就是对证中药治疗RA热证"药-证对应"的分子生物学机制之一,具体机制需要进一步验证。We built and analyzed the molecular networks of RA with heat pattern and the target proteins of herbs corresponding to RA with heat pattern,in order to find the molecular mechanism of ＇herbs-pattern correspondence＇ in RA with heat pattern in Traditional Chinese Medicine.We searched for the most commonly used herbs on heat pattern RA by literatures mining;searched for the target proteins of herbs corresponding to heat pattern RA in PubChem database;collected the peripheral blood CD4＋T cells in both heat pattern RA patients and healthy persons,in order to find the differential expression genes by microarray.We built the network of heat pattern RA and the network of target proteins of herbs corresponding with heat pattern;by ＇Ingenuity Pathway Analysis＇,to compare and analyze the two networks.We got 4 commonly used herbs treating heat pattern RA： Cortex phellodendri,Rhizoma Anemarrhenae,Rhizoma Atractylodis and Radix achyranthis bidentatae by literatures mining.There were 123 target proteins of the four herbs corresponding to heat pattern from PubChem.21 differential expression genes between heat pattern RA patients and healthy persons were found.The networks of heat pattern RA and the target proteins of herbs corresponding to heat pattern were built by IPA.There were four common canonical pathways between them： GM-CSF Signaling,CLTA4 Signaling in Cytotoxic T Lymphocytes,T cell Receptor Signaling and CD28 Signaling in T Helper cells,which were related with the cell survival,cell-mediated immune response,inflammatory response and so on.The results show that the four common canonical pathways： GM-CSF Signaling,CLTA4 Signaling in Cytotoxic T Lymphocytes,T cell Receptor Signaling and CD28 Signaling in T Helper cells,may be the molecular mechanism of ＇herbs-pattern correspondence＇ in RA with heat pattern,but the confirmation of it still be needed further.

关 键 词：网络药理学 类风湿性关节炎 热证 中药 药-证对应 

分 类 号：R222.19[医药卫生—中医基础理论]