药学学报, 2018, 53(9): 1387-1397
引用本文:
李玮婕, 卢建秋, 毛霞, 郭秋岩, 王晓月, 郭敏群, 张彦琼, 林娜. 基于靶标网络分析的治痹寒热经方抗类风湿关节炎作用机制对比研究[J]. 药学学报, 2018, 53(9): 1387-1397.
LI Wei-jie, LU Jian-qiu, MAO Xia, GUO Qiu-yan, WANG Xiao-yue, GUO Min-qun, ZHANG Yan-qiong, LIN Na. A comparative study on the mechanisms of two classical herbal formulae for rheumatoid arthritis applying cold and heat patterns based on target network[J]. Acta Pharmaceutica Sinica, 2018, 53(9): 1387-1397.

基于靶标网络分析的治痹寒热经方抗类风湿关节炎作用机制对比研究
李玮婕1,2, 卢建秋1,3, 毛霞2, 郭秋岩2, 王晓月2, 郭敏群2, 张彦琼2, 林娜2
1. 北京中医药大学中药学院, 北京 100102;
2. 中国中医科学院中药研究所, 北京 100700;
3. 北京中医药大学图书馆, 北京 100029
摘要:
乌头汤和白虎加桂枝汤分别为寒、热痹的代表经方,临床治疗类风湿关节炎(rheumatoid arthritis,RA)疗效确切,但其作用特点及潜在药理机制均尚未明确。本研究借助大鼠佐剂性关节炎(adjuvant-induced arthritis,AIA)模型,开展全基因组表达谱芯片检测和网络药理学挖掘的整合研究。结果表明,乌头汤和白虎加桂枝汤均可有效降低AIA大鼠的发病率并改善关节炎症状,但两者对冷痛敏和热辐射反应的干预效果有明显差异。进一步的靶标网络分析发现,乌头汤和白虎加桂枝汤中分别筛选出106和132个抗RA效应基因,这些抗RA的关键候选靶标均分别参与矫正RA相关炎症-免疫失衡网络,但前者还可调节机体激素和能量代谢反应。本研究对比分析了寒热痹经方抗RA作用靶点和通路的异同点,为深入揭示经方治痹功效的生物学内涵提供了初步的科学依据。
关键词:    乌头汤      白虎加桂枝汤      类风湿关节炎      网络分析      作用机制     
A comparative study on the mechanisms of two classical herbal formulae for rheumatoid arthritis applying cold and heat patterns based on target network
LI Wei-jie1,2, LU Jian-qiu1,3, MAO Xia2, GUO Qiu-yan2, WANG Xiao-yue2, GUO Min-qun2, ZHANG Yan-qiong2, LIN Na2
1. School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 100102, China;
2. Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China;
3. Library of Beijing University of Chinese Medicine, Beijing 100029, China
Abstract:
Wu-tou decoction (WTD) and Baihu-Guizhi decoction (BHGZD) as described in the Synopsis of the Golden Chamber have been used extensively for the treatment of rheumatoid arthritis (RA) with apparent therapeutic efficacy. However, characteristics of pharmacological effects and their underlying molecular mechanisms have not been fully elucidated due to a lack of appropriate scientific methodology. In the current study, we performed an integrative approach applying gene expression profiling and network analysis to examine the therapeutic effects and molecular mechanisms of WTD and BHGZD based on adjuvant-induced arthritis (AIA) animal model. Results demonstrated that both WTD and BHGZD could relieve the severity of arthritis in AIA rats, while the significant differences were observed in the changes of the withdrawal response scores and latency time of AIA rats treated with WTD and BHGZD. Mechanistically, our network pharmacology-based investigation demonstrated that the major candidate targets of WTD and BHGZD were significantly associated with several inflammation-immune regulatory pathways, such as Toll-like receptor signaling pathway, T cell receptor signaling pathway, cytokine-cytokine receptor interaction, chemokine signaling pathway, B cell receptor signaling pathway, antigen processing and presentation, Fc epsilon RI signaling pathway, natural killer cell mediated cytotoxicity, as well as leukocyte transendothelial migration. In particular, the major candidate targets of WTD were also involved in the regulation of hormone and energy metabolism, which might be imbalanced during RA progression. In conclusion, the current study revealed differences and similarities regarding the effects and network regulatory mechanisms of WTD and BHGZD. These findings may present a scientific basis for elucidation of mechanisms by which WTD and BHGZD alleviates RA.
Key words:    Wu-tou decoction    Baihu-guizhi decoction    rheumatoid arthritis    network analysis    mechanism   
收稿日期: 2018-06-01
DOI: 10.16438/j.0513-4870.2018-0519
基金项目: 国家自然科学基金资助项目(81630107,81673834);中央级公益性科研院所基本科研业务费专项资金资助(L2017018).
通讯作者: 张彦琼,Tel:86-10-64014411-2869,E-mail:yqzhang@icmm.ac.cn;林娜,E-mail:nlin@icmm.ac.cn
Email: yqzhang@icmm.ac.cn;nlin@icmm.ac.cn
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