基于疾病模块分析的大株红景天注射液治疗冠心病心绞痛气虚血瘀证的研究

Study on the Treatment of Qi Deficiency and Blood Stasis Syndrome of Coronary Heart Disease Angina Pectoris with Sofren Injection Based on Disease Module Analysis

    摘要
  • 摘要:
    目的 揭示大株红景天注射液治疗冠心病心绞痛气虚血瘀证的药理机制，并运用细胞实验初步验证预测结果的可靠性。
    方法 从生物医学数据库和国内外文献中筛选出大株红景天注射液的主要化学成分及其作用靶点；通过GeneCards数据库、MalaCards数据库筛选出气虚血瘀证、心绞痛基因，采用DIAMOnD算法构建心绞痛疾病模块；对“心绞痛-气虚血瘀证-大株红景天注射液”网络的核心靶点进行基因功能富集分析，得到关键通路。最后，进行细胞实验验证大株红景天注射液对缺氧H9C2心肌细胞关键通路蛋白表达的影响。
    结果 筛选出大株红景天注射液主要的化学成分7个，共获得靶点362个；筛选出232个已知心绞痛基因，通过构建心绞痛疾病模块，增加了100个预测得到的心绞痛基因；得到气虚血瘀证症状相关基因2 960个。网络拓扑分析得到大株红景天注射液治疗冠心病心绞痛气虚血瘀证的核心靶点有STAT3、EGFR、TNF、IL-6等共30个；基因功能富集分析获得通路82条。结合以往文献研究分析显示STAT3靶点和JAK2/STAT3通路可能是大株红景天注射液治疗冠心病心绞痛气虚血瘀证的关键作用通路。细胞实验结果显示，与模型组比较，SI组及尼可地尔组JAK2、STAT3的mRNA表达均显著降低(P < 0.05)；JAK2、STAT3的蛋白表达显著下降(P < 0.05)。
    结论 通过疾病模块和细胞实验验证发现STAT3是冠心病心绞痛气虚血瘀证病理机制的关键基因，JAK2/STAT3是大株红景天注射液治疗冠心病心绞痛气虚血瘀证的核心通路，表明了本研究结合疾病模块进行药物治疗病证的有效性和新颖性。

     

    Abstract:
    OBJECTIVE To reveal the pharmacological mechanism of Sofren Injection in the treatment of Qi deficiency and blood stasis syndrome of angina pectoris in coronary heart disease, and to preliminarily verify the reliability of the prediction results by cell experiments.
    METHODS Firstly, we screened the main chemical components of Sofren injection and their targets from biomedical databases and literature. Then, using the DIAMOnD algorithm, we constructed the angina disease module by screening Qi deficiency and blood stasis syndrome-related genes from the GeneCards and MalaCards databases. Next, we conducted gene functional enrichment analysis of the core targets in the "angina pectoris-Qi deficiency and blood stasis-Sofren Injection" network to identify key pathways. Finally, we performed cell experiments to verify the effect of Sofren Injection on the expression of key pathway proteins in hypoxic H9C2 cardiomyocytes.
    RESULTS We identified 7 main chemical components of Sofren Injection, targeting a total of 362 genes. We screened 232 known angina pectoris-related genes and added 100 predicted genes by constructing the angina pectoris disease module. A total of 2 960 genes related to Qi deficiency and blood stasis syndrome were obtained. Network topological analysis revealed 30 core targets for Sofren Injection in treating coronary heart disease angina pectoris with Qi deficiency and blood stasis syndrome, including STAT3, EGFR, TNF, and IL-6. Gene functional enrichment analysis identified 82 pathways. Literature analysis combined with the results indicated that STAT3 and the JAK2/STAT3 pathway might be key pathways for Sofren Injection in treating coronary heart disease angina pectoris with Qi deficiency and blood stasis syndrome. Cell experimental results showed significant decreases in mRNA and protein expression of JAK2 and STAT3 in the SI group and the nicorandil group compared to the model group (P < 0.05).
    CONCLUSION Disease module analysis and cell experiments confirm that STAT3 is a key gene in the pathological mechanism of coronary heart disease angina pectoris with Qi deficiency and blood stasis syndrome, and the JAK2/STAT3 pathway is a core pathway for Sofren Injection in treating this condition. This study demonstrates the effectiveness and novelty of combining disease module for mining the treatment of TCM formulas with specific disease and syndrome.

     

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