Yang Guang, Zhou Si-Yuan, Wang Jie, Hu Jun, Pan Ju-Hua
Guang'anmen Hospital, China Academy of Chinese Medical Sciences Beijing 100053, China.
Zhongguo Zhong Yao Za Zhi. 2023 Apr;48(7):1908-1915. doi: 10.19540/j.cnki.cjcmm.20221114.701.
This study aimed to analyze the biological foundation and biomarkers of stable coronary heart disease(CHD) with phlegm and blood stasis(PBS) syndrome based on RNA-seq and network pharmacology. Peripheral blood nucleated cells from five CHD patients with PBS syndrome, five CHD patients with non-PBS syndrome, and five healthy adults were collected for RNA-seq. The specific targets of CHD with PBS syndrome were determined by differential gene expression analysis and Venn diagram analysis. The active ingredients of Danlou Tablets were screened out from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, and the "component-target" prediction was completed through PubChem and SwissTargetPrediction. The "drug-ingredient-target-signaling pathway" network of Danlou Tablets against CHD with PBS syndrome was optimized by Cytoscape software. After the target biomarkers were identified, 90 participants were enrolled for diagnostic tests, and 30 CHD patients with PBS syndrome were included in before-and-after experiment to determine the therapeutic effect of Danlou Tablets on those targets. As revealed by RNA-seq and Venn diagram analysis, 200 specific genes were identified for CHD with PBS syndrome. A total of 1 118 potential therapeutic targets of Danlou Tablets were predicted through network pharmacology. Through integrated analysis of the two gene sets, 13 key targets of Danlou Tablets in the treatment of CHD with PBS syndrome were screened out, including CSF1, AKR1C2, PDGFRB, ARG1, CNR2, ALOX15B, ALDH1A1, CTSL, PLA2G7, LAP3, AKR1C3, IGFBP3, and CA1. They were presumably the biomarkers of CHD with PBS syndrome. The ELISA test further showed that CSF1 was significantly up-regulated in the peripheral blood of CHD patients with PBS syndrome, and was significantly down-regulated after Danlou Tablets intervention. CSF1 may be a biomarker for CHD with PBS syndrome, and it is positively correlated with the severity of the disease. The diagnostic cut-off of CSF1 for CHD with PBS syndrome was 286 pg·mL~(-1).
本研究旨在基于RNA测序和网络药理学分析稳定型冠心病痰瘀证的生物学基础和生物标志物。收集5例冠心病痰瘀证患者、5例非痰瘀证冠心病患者及5例健康成年人的外周血有核细胞进行RNA测序。通过差异基因表达分析和韦恩图分析确定冠心病痰瘀证的特异性靶点。从中药系统药理学数据库及分析平台筛选丹蒌片的活性成分，并通过PubChem和SwissTargetPrediction完成“成分-靶点”预测。利用Cytoscape软件优化丹蒌片治疗冠心病痰瘀证的“药物-成分-靶点-信号通路”网络。确定靶点生物标志物后，纳入90名参与者进行诊断试验，并选取30例冠心病痰瘀证患者进行前后试验，以确定丹蒌片对这些靶点的治疗效果。RNA测序和韦恩图分析显示，确定了200个冠心病痰瘀证的特异性基因。通过网络药理学预测了丹蒌片总共1118个潜在治疗靶点。通过对两个基因集的综合分析，筛选出丹蒌片治疗冠心病痰瘀证的13个关键靶点，包括CSF1、AKR1C2、PDGFRB、ARG1、CNR2、ALOX15B、ALDH1A1、CTSL、PLA2G7、LAP3、AKR1C3、IGFBP3和CA1。它们可能是冠心病痰瘀证的生物标志物。酶联免疫吸附试验进一步表明，CSF1在冠心病痰瘀证患者外周血中显著上调，丹蒌片干预后显著下调。CSF1可能是冠心病痰瘀证的生物标志物，且与疾病严重程度呈正相关。冠心病痰瘀证的CSF1诊断临界值为286 pg·mL⁻¹。
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