摘要
探索清肺消炎丸抗炎的网络调控机制。采用UPLC Q-TOF鉴定清肺消炎丸的化学成分,利用Molinspiration、PharmMapper和KEGG等生物信息学手段对其进行吸收、靶点及作用通路的预测分析;并结合豚鼠哮喘模型和人支气管上皮细胞炎症模型,分别采用基因芯片和实时定量PCR技术研究其对相关炎症基因表达的影响。预测结果显示,在所鉴定的55种化学成分中有24种可被吸收,其中19种可能通过干预HRAS、PDPK1等11个靶点分别作用于炎症相关的9条通路。实验结果表明,清肺消炎丸能显著改善肺组织炎症因子浸润,通过影响ERK1等基因的表达进而干预黏着斑、Fc epsilon RI、Toll样受体、NK细胞介导的细胞毒以及ERK/MAPK等5条通路参与抗炎反应;牛蒡子苷元、胆酸、芥子酸等药效代表性成分分别通过干预ERK/MAPK、黏着斑和Fc epsilon RI等信号通路发挥了抗炎作用。本文建立了"药物-靶点-通路-网络"的研究模式,初步揭示了清肺消炎丸抗炎的多维调控机制,为中药复方的研究提供了新的思路和方法。
This study aims to clarify out the anti-inflammatory mechanism of Qingfei Xiaoyan Wan. Chemical constituents of Qingfei Xiaoyan Wan identified by UPLC Q-TOF, were submit to Molinspiration, PharmMapper and KEGG bioinformatics softwares for predicting their absorption parameters, target proteins and related pathways respectively; and the gene chip and real time-PCR were carried out to investigate the expression of inflammatory genes on lung tissue of guinea pigs or human bronchial epithelial cell lines. The predicted results showed that 19 of the 24 absorbable constituents affected at 9 inflammation-related pathways through 11 protein targets; Qingfei Xiaoyan Wan treatment can significantly reduce the infiltration of cytokines through ERK1 gene and 5 inflammatory pathways （Focal adhesion, Fc epsilon RI, Toll-like receptors, NK cell-mediated cytotoxic, and ERK/MAPK）. The results of real time-PCR further confirmed that the anti-inflammatory effects of Qingfei Xiaoyan Wan were due to active ingredients such as arctigenin, cholic acid and sinapic acid intervened focal adhesion, Fc epsilon RI signaling and ERK/MAPK pathways. The novel approach of ＇drug-target-pathway＇ will present an effective strategy for the study of traditional Chinese medicines.
出处
《药学学报》
CAS
CSCD
北大核心
2013年第5期686-693,共8页
Acta Pharmaceutica Sinica
基金
国家自然科学基金资助项目(81173638
81102835)
