目的 探讨肠炎宁颗粒的成分及其对阿司匹林致肠黏膜损伤大鼠的药效和和代谢组学分子协同机制。方法 通过UPLC-LTQ-Orbitrap-MS法鉴定肠炎宁颗粒的化学成分。36只SD大鼠随机分为对照组、模型组、阳性对照组（奥美拉唑2.08 mg/kg＋瑞巴派特31.25 mg/kg）和肠炎宁颗粒高、中、低剂量（0.96、0.48、0.24 g/kg）组，采用阿司匹林诱导大鼠肠黏膜损伤模型，给予药物干预后，检测各组大鼠血清中二胺氧化酶（diamine oxidase，DAO）和溶菌酶（lysozyme，LZM）活性；检测血清、胃、小肠组织中炎性因子水平；采用苏木素-伊红（HE）染色观察胃、小肠组织病理学变化。基于代谢组学筛选差异代谢物并进行代谢通路分析。结果 肠炎宁颗粒共鉴定出52个化合物，以黄酮类和有机酸类成分为主。与对照组比较，模型组大鼠血清中DAO活性显著升高（P＜0.001），LZM活性显著降低（P＜0.001），血清、胃、小肠组织中促炎因子白细胞介素-1β（interleukin-1β，IL-1β）、IL-6、肿瘤坏死因子-α（tumor necrosis factor-α，TNF-α）水平显著升高（P＜0.05、0.01、0.001），抑炎因子IL-4、IL-10水平显著降低（P＜0.05、0.01、0.001），胃和小肠组织出现损伤。与模型组比较，肠炎宁颗粒组血清中DAO活性显著降低（P＜0.05、0.01），LZM活性显著升高（P＜0.05、0.01），血清、胃、小肠组织中IL-1β、IL-6、TNF-α水平显著降低（P＜0.05、0.01、0.001），IL-4、IL-10水平显著升高（P＜0.05、0.01、0.001），胃和小肠组织损伤有所缓解。代谢组学结果显示，肠炎宁颗粒干预后共有33个差异代谢物，涉及多条代谢途径。结论 肠炎宁颗粒以黄酮类和有机酸类成分为主，通过调节DAO、LZM及炎症因子，显著改善阿司匹林致大鼠肠黏膜损伤。代谢组学证实其通过多通路（苯丙氨酸等氨基酸代谢、磷酸酶代谢）协同作用，为肠道黏膜损伤的治疗提供依据。

Objective To explore the components of Changyanning Granules (肠炎宁颗粒) and their pharmacological effects on aspirin-induced intestinal mucosal injury in rats, as well as the molecular synergistic mechanism of metabolomics. Methods The chemical components of Changyanning Granules were identified using UPLC-LTQ-Orbitrap-MS method. Thirty-six SD rats were randomly divided into control group, model group, positive group (omeprazole 2.08 mg/kg + rebamipide 31.25 mg/kg), high-, medium-, and low-dose (0.96, 0.48, 0.24 g/kg) of Changyanning Granules. Aspirin was used to induce intestinal mucosal injury in rats. After drug intervention, the activities of diamine oxidase (DAO) and lysozyme (LZM) in serum of rats in each group were detected; The levels of inflammatory factors in serum, stomach and small intestine tissues were detected; Hematoxylin eosin (HE) staining was used to observe the pathological changes in stomach and small intestine tissues. Differential metabolites were screened based on metabolomics for metabolic pathway analysis. Results A total of 52 compounds were identified in Changyanning Granules, mainly composed of flavonoids and organic acids. Compared with control group, DAO activity in serum of rats in model group was significantly increased (P < 0.001), and LZM activity was significantly decreased (P < 0.001). The levels of pro-inflammatory cytokines interleukin-1β (IL-1β), IL-6 and tumor necrosis factor-α (TNF-α) in serum, stomach and small intestine tissues were significantly increased (P < 0.05, 0.01, 0.001), levels of anti-inflammatory factors IL-4 and IL-10 were significantly decreased (P < 0.05, 0.01, 0.001). Damages were observed in stomach and small intestine tissues. Compared with model group, DAO activity in serum of rats in Changyanning Granules groups was significantly reduced (P < 0.05, 0.01), and LZM activity was significantly increased (P < 0.05, 0.01). The levels of IL-1β, IL-6 and TNF-α in serum, stomach and small intestine tissues were significantly reduced (P < 0.05, 0.01, 0.001), and levels of IL-4 and IL-10 were significantly increased (P < 0.05, 0.01, 0.001). The damage to the stomach and small intestine tissues was alleviated. Metabolomics results showed that there were a total of 33 differential metabolites involved in multiple metabolic pathways after intervention with Changyanning Granules. Conclusion Changyanning Granules are mainly composed of flavonoids and organic acids. Changyanning Granules significantly improve aspirin-induced intestinal mucosal injury in rats by regulating DAO, LZM and inflammatory factors. Metabolomics confirms that it works synergistically through multiple pathways (amino acid metabolism such as phenylalanine, phosphatase metabolism), providing a basis for the treatment of intestinal mucosal injury.

R285.5

北京市自然科学基金资助项目（7254509）