基于网络药理学探讨外用通腑汤治疗术后肠梗阻的作用机制

作者：刘静文，史晓光，左禧萌，王玉坤

单位：北京中医药大学东直门医院，北京 100700

引用：引用：刘静文，史晓光，左禧萌，王玉坤.基于网络药理学探讨外用通腑汤治疗术后肠梗阻的作用机制[J].中医药导报,2025,31(12):75-82.

DOI：10.13862/j.cn43-1446/r.2025.12.012

PDF： 下载PDF

摘要：

目的：基于网络药理学及动物实验方法，探讨外用通腑汤治疗术后肠梗阻（POI）的可能作用机制。方法：利用数据库筛选通腑汤的活性化合物、作用靶点及POI的治疗靶点，通过映射药物和疾病靶点获得交集靶点，构建交集靶点的蛋白质相互作用PPI网络和药物-活性化合物-靶点网络图，后对交集靶点进行GO和KEGG富集分析。将27只C57小鼠分为模型组、假手术组和通腑汤组，每组9只，模型组及通腑汤组于无菌条件下模拟临床全小肠探查手术，假手术组仅行开腹翻肠操作。通腑汤组将通腑汤贴剂粘于小鼠肩胛部皮肤，每24 h换药1次。术后1、3、5  d比较各组小鼠小肠墨汁推进率；酶联免疫吸附试验（ELISA）法检测血清中IL-6、TNF-α、CRP、CCL2、IL-1β、IL-10水平；HE染色观察结肠组织形态；蛋白质印迹法（Western blotting）检测术后24、72 h结肠组织中JAK2、STAT3的表达。结果：通过网络药理学为通腑汤构建了包含11种中药、74种活性化合物和101种靶蛋白的相互作用网络。对交集基因进行GO和KEGG富集分析，GO注释显示通腑汤治疗POI涉及的生物过程主要与对脂多糖的反应等有关；细胞组成与细胞膜等的生理功能有关；分子功能主要涉及溶酶体等。KEGG富集分析显示其主要通过调控TNF、HIF-1、IL-17、PI3K-Akt、ErbB、MAPK、cAMP、趋化因子、JAK-STAT等通路治疗POI。在术后第1天和第3天，通腑汤组小鼠小肠墨汁推进率显著高于模型组（P<0.05）；与模型组比较，通腑汤组小鼠结肠黏膜上皮结构更完整，结肠绒毛和肌肉组织中嗜酸性粒细胞浸润减少，血管舒张倾向减弱。与模型组比较，外用通腑汤组小鼠IL-6、TNF-α、CRP及IL-10水平均降低（P<0.05或P<0.01）；与模型组比较，通腑汤组小鼠结肠组织中术后24 h的STAT3及术后72 h的JAK2、STAT3表达水平均降低（P<0.05或P<0.01）。结论：外用通腑汤对IL-6、TNF-α、CRP及IL-10的表达产生影响，可抑制JAK2-STAT3信号通路，可能通过调控免疫炎症反应、氧化应激及细胞凋亡等机制治疗POI。

关键词：术后肠梗阻；通腑汤；网络药理学；动物实验；JAK2-STAT3信号通路；小鼠

Abstract：

Objective: To explore the possible mechanism of external Tongfu decoction in the treatment of postoperative ileus (POI)  based on network pharmacology and animal experiments. Methods: The active compounds, action targets, and therapeutic targets of the POI associated with Tongfu decoction were identified using a comprehensive database. The intersection of drug and disease targets was established through mapping techniques. Subsequently, a protein-protein interaction (PPI) network for the intersecting targets was constructed alongside a network diagram illustrating the relationships between drugs, active compounds, and their respective targets. Following this, Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analyses were conducted on the intersecting targets. A total of 27 C57 mice were randomly assigned to model group, sham operation group and Tongfu decoction group, with 9 mice in each group. The model group and Tongfu decoction group underwent a comprehensive exploration of the small intestine under sterile conditions, while the sham operation group only received laparotomy and intestinal manipulation. In the Tongfu decoction group, patches containing Tongfu decoction were affixed to the skin overlying the scapular region of each mouse, with patch changes occurring every 24 hours. On days 1, 3, and 5 post-surgery, the intestinal ink propulsion rates were compared among all groups. Serum levels of IL-6, TNF-α, CRP, CCL2, IL-1β, and IL-10 were measured using enzyme-linked immunosorbent assay (ELISA). Additionally, colon tissue morphology was assessed through hematoxylin-eosin (HE) staining. The expression levels of JAK2 and STAT3 in colon tissue at 24 hours and 72 hours after surgery were evaluated via Western blotting. Results: An interaction network comprising 11 traditional Chinese medicines, 74 active compounds, and 101 target proteins was established for Tongfu decoction through the application of network pharmacology. GO and KEGG enrichment analyses of the intersecting genes indicated that the biological processes associated with the treatment of POI using Tongfu decoction were primarily linked to responses to lipopolysaccharides. The cellular composition was found to be related to physiological functions of cell membranes. Molecular functions predominantly involved lysosomal activity. The KEGG enrichment analysis revealed that Tongfu decoction mainly modulated pathways such as TNF, HIF-1, IL-17, PI3K-Akt, ErbB, MAPK, cAMP, chemokines, JAK-STAT and others in its therapeutic approach towards POI. On the first and third day post-surgery, the intestinal ink propulsion rate in mice of Tongfu decoction group was significantly higher than that of the model group (P<0.05). In comparison to the model group, the colonic mucosal epithelial structure of mice in Tongfu decoction group exhibited greater integrity, accompanied by a reduction in eosinophil infiltration within both colonic villi and muscle tissue, as well as a diminished tendency for vasodilation. Furthermore, when compared to the model group, levels of IL-6, TNF-α, CRP, and IL-10 were all significantly decreased in mice of Tongfu decoction group (P<0.05 or P<0.01). Additionally, compared with the model group, the expression levels of STAT3 at 24 hours post-operation and JAK2 and STAT3 at 72 hours post-operation in the colon tissue of mice in the Tongfu decoction group were decreased (P<0.05 or P<0.01). Conclusion: The external application of Tongfu decoction influences the expression levels of IL-6, TNF-α, CRP and IL-10. It inhibits the JAK2-STAT3 signaling pathway and may provide therapeutic benefits for POI through mechanisms such as modulation of immune inflammatory responses, oxidative stress regulation, and apoptosis induction.

Key words：postoperative ileus; Tongfu decoction; network pharmacology; animal experiments; JAK2-STAT3 signaling pathway; mice

发布时间：2025-12-31

点击量：6