目的 基于胃肠安丸ig给药后结肠组织的基质辅助激光解吸/电离飞行时间质谱成像（matrix-assisted laser desorption/ ionization time-of-flight mass spectrometry imaging，MALDI-TOF-MSI）技术检测结果、网络药理学预测及质量标志物（quality marker，Q-Marker）“五原则”，筛选胃肠安丸治疗腹泻型肠易激综合征（irritable bowel syndrome with diarrhea，IBS-D）的潜在Q-Marker，并建立胃肠安丸中潜在Q-Marker的多成分定量方法。方法 将SD大鼠按照25.12 mg/kg的剂量进行ig给药，ig后3、6、8、12、24 h取结肠组织，基于MALDI-TOF-MSI技术识别胃肠安丸关键活性成分以及其在结肠组织中的代谢转化产物；依据胃肠安丸体内暴露成分的预测靶点与IBS-D的疾病靶点取交集构建蛋白质-蛋白质相互作用（protein-protein interaction，PPI）网络筛选出核心潜在作用靶点，根据核心潜在作用靶点筛选出胃肠安丸治疗IBS-D的核心活性成分，再结合Q-Marker“五原则”筛选出胃肠安丸治疗IBS-D的潜在Q-Marker，最后针对潜在Q-Marker建立多成分定量方法。结果 依据MALDI-TOF-MSI检测结果共得到胃肠安丸22个体内暴露成分，将这22个成分的预测靶点与IBS-D的疾病靶点取交集得到70个交集靶点，基于度值排名前10的核心潜在作用靶点与Q-Marker“五原则”筛选出柚皮苷、新橙皮苷、大黄酚、大黄素、和厚朴酚与厚朴酚为胃肠安丸治疗IBS-D的潜在Q-Marker，使用分子对接对其结果进行验证，建立了这6个潜在Q-Marker的多成分定量方法。结论 确定了胃肠安丸治疗IBS-D的潜在Q-Marker，为中药复方体内暴露成分鉴定、Q-Marker筛选及其质量控制研究提供参考。

Objective To screen potential quality markers (Q-Marker) of Weichang’an Pills (WP, 胃肠安丸) for the treatment of diarrhea-predominant irritable bowel syndrome (IBS-D) based on matrix-assisted laser desorption/ionization time-of-flight mass spectrometry imaging (MALDI-TOF-MSI) detection of colon tissues after intragastric administration of WP, network pharmacology prediction, and the “Five Principles” of Q-Marker, and to establish a multi-component quantitative method for the potential markers in WP. Methods SD rats were intragastrically administered WP at a dose of 25.12 mg/kg. Colon tissues were collected at 3, 6, 8, 12, 24 h after administration. Key active constituents of WP and their metabolic transformation products in colon tissues were identified using MALDI-TOF-MSI. The intersection of the predicted targets of in vivo exposed WP constituents and IBS-D-related disease targets was used to construct a protein-protein interaction (PPI) network and screen core targets. Core active constituents of WP for the treatment of IBS-D were then identified based on these core targets. Potential Q-Marker of WP for IBS-D treatment were further screened by integrating the “Five Principles” of Q-Marker, and a multi-component quantitative method was established for the selected potential Q-Marker. Results A total of 22 in vivo exposed constituents of WP were obtained based on MALDI-TOF-MSI detection. The predicted targets of these 22 constituents were intersected with IBS-D-related disease targets, yielding 70 overlapping targets. Based on the top 10 core targets ranked by Degree value and the “Five Principles” of Q-Marker, naringin, neohesperidin, chrysophanol, emodin, honokiol, and magnolol were screened as potential Q-Marker of WP for the treatment of IBS-D. The screening results were verified by molecular docking, and a multi-component quantitative method was finally established for these six potential Q-Marker. Conclusion Potential Q-Marker of WP for the treatment of IBS-D were identified. This strategy provides a reference for the identification of in vivo exposed constituents, Q-Marker screening, and quality control research of traditional Chinese medicine compound preparations.

R283.6