基于网络药理学和分子对接研究益脾通便汤治疗功能性便秘的作用机制-现代医学

基于网络药理学和分子对接研究益脾通便汤治疗功能性便秘的作用机制

单位：1. 淮安市中医院肛肠科, 江苏淮安 223000;
2. 淮安市第二人民医院检验科, 江苏淮安 223000

关键词：功能性便秘益脾通便汤肠道菌群 5-羟色胺4受体肠道酶活性网络药理学分子对接

分类号：R289.5

出版年·卷·期（页码）：2025·53·第九期（1390-1400）

摘要：

目的： 通过观察择时应用益脾通便汤对功能性便秘(脾虚型)大鼠的疗效，运用网络药理学和分子对接方法探讨益脾通便汤治疗功能性便秘的作用机制。方法： 随机将100只昆明种大鼠分成正常组、模型组、1组、2组及PEG4000组，每组各20只。除正常组外，其余4组大鼠均予复方地芬诺酯混悬液灌胃进行便秘模型造模。造模成功后，1、2组大鼠分别在巳时(9~11 a.m.)和辰时(7~9 a.m.)灌胃益脾通便汤，PEG4000组大鼠灌胃聚乙二醇4000散，正常组和模型组则以常温的蒸馏水灌胃，每组大鼠均干预2周。分析并比较5组大鼠体质量、小肠推动运动能力、结肠5-羟色胺4(5-HT4)受体活性及肠道酶活性等相关指标；基于肠道微生物组学结果，应用网络药理学及分子对接方法，探讨益脾通便汤治疗功能性便秘的作用机制。结果： 1、2组大鼠体质量、炭末推进长度、推进率、纤维素酶活性及5-HT4受体蛋白水平均显著优于模型组，木聚糖酶活性低于模型组(均P<0.01)。相较于辰时灌胃，益脾通便汤巳时灌胃能够较为明显的改善便秘大鼠的肠道菌群结构，尤以乳酸菌属最为显著。网络药理学结果表明，益脾通便汤和功能性便秘的共同靶点为26个，基于GO富集和KEGG通路分析发现，益脾通便汤治疗功能型便秘作用机制可能与钙离子信号、癌症、cGMP-PKG信号、PI3K-Akt信号等通路相关。分子对接结果表明，排名前5位核心靶点分别与益脾通便汤关键化合物成分木犀草素、常春藤皂苷元、异鼠李素、柚皮素、甘油对接吻合度较好。结论： 益脾通便汤可通过调节肠道菌群，显著增加乳酸菌属数量，改善肠道微环境及酶活性，增加肠道动力和水分治疗功能性便秘。

Objective: To observe the therapeutic effect of Yipi Tongbian decoction administered at specific time points on rats with functional constipation(spleen deficiency type), and to explore its mechanism of action using network pharmacology and molecular docking. Methods: One hundred Kunming rats were randomly divided into five groups(n=20 per group): normal control, model control, group 1, group 2 and PEG4000 group. Except for the normal control group, all other groups were administered compound diphenoxylate suspension via gavage to establish the constipation model. After successful modeling, group 1 and group 2 received Yipi Tongbian decoction at Si time(9-11 a.m.) and Chen time(7-9 a.m.), respectively. The PEG4000 group received polyethylene glycol 4000, while the normal and model control groups received warm distilled water. All interventions lasted for two weeks. Body weight, small intestinal propulsion ability, colonic 5-hydroxytryptamine 4(5-HT4) receptor activity, and intestinal enzyme activity were measured and compared among the five groups. Based on gut microbiomic results, network pharmacology and molecular docking were applied to investigate the mechanism of Yipi Tongbian decoction in treating functional constipation. Results: Body weight, charcoal propulsion length, propulsion rate, cellulase activity, and 5-HT4 receptor protein levels in groups 1 and 2 were significantly better than those in the model control group, while xylanase activity was lower than that in the model control group(all P<0.01). Compared to administration at Chen time, Yipi Tongbian decoction given at Si time more markedly improved the gut microbiota structure in constipated rats, particularly increasing the abundance of Lactobacillus. Network pharmacology revealed 26 common targets between Yipi Tongbian decoction and functional constipation. GO enrichment and KEGG pathway analyses indicated that the mechanism of Yipi Tongbian decoction may involve calcium signaling, cancer, cGMP-PKG signaling, PI3K-Akt signaling, and other pathways. Molecular docking showed that the top five core targets had strong binding affinities with key active compounds of Yipi Tongbian decoction, including luteolin, hederagenin, isorhamnetin, naringenin, and glycerol. Conclusion: Yipi Tongbian decoction can effectively treat functional constipation by modulating the gut microbiota, significantly increasing Lactobacillus abundance, improving the intestinal microenvironment and enzyme activity, and enhancing intestinal motility and hydration.

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