目的 基于网络药理学和动物实验探讨人参健脾丸防治化疗性肠黏膜炎的有效成分及潜在作用靶点和通路。方法 通过开放的中药数据库和疾病数据平台收集人参健脾丸的活性成分及治疗化疗性肠黏膜炎的潜在作用靶点，通过STING在线分析平台构建蛋白相互作用（PPI）网络，通过基因本体（GO）功能富集分析和京都基因与基因组百科全书（KEGG）通路富集分析探讨人参健脾丸治疗化疗性肠黏膜炎的有效成分及可能的作用靶点和通路。将大鼠随机分为对照组、模型组、谷氨酰胺散组、人参健脾丸（4.8、2.4、1.2 g/kg）组，每组12只。末次给药后24 h取材。观察大鼠一般状态、体质量、腹泻评分；血清炎性因子的变化情况；肠组织病理改变情况以及Toll样受体（TLR）/核因子（NF-κB）等的变化情况。结果 网络药理学研究结果显示，共筛选出人参健脾丸的主要活性成分76个，其中槲皮素、山柰酚和柚皮素对应靶点最多，可能是人参健脾丸治疗化疗性肠黏膜炎的有效成分。其用于肠黏膜炎潜在靶点蛋白152个，主要作用靶点蛋白涉及丝裂原活化蛋白激酶（MAPK）3、蛋白激酶B1（Akt1）、肿瘤坏死因子（TNF）、白细胞介素（IL）-6、NF-κB等，作用通路涉及磷脂酰肌醇3-激酶（PI3K）/Akt信号通路、IL-17信号通路、肿瘤坏死因子信号通路、MAPK信号通路等。动物实验结果显示：与模型组比较，人参健脾丸4.8 g/kg组大鼠体质量显著升高（P＜0.05）；人参健脾丸（4.8、1.2 g/kg）组大鼠腹泻评分显著降低（P＜0.05、0.01）；人参健脾丸（4.8、2.4 g/kg）组大鼠肠组织病理评分显著降低（P＜0.01）；人参健脾丸4.8 g/kg组大鼠血清中TNF-α和IL-1β水平均显著降低（P＜0.05、0.01）；人参健脾丸2.4 g/kg组大鼠血清中IL-1β显著降低（P＜0.05）；人参健脾丸（4.8、1.2 g/kg）组大鼠肠组织TLR4、NF-κB蛋白表达显著降低（P＜0.05、0.01）。结论 人参健脾丸具有多成分、多靶点、多通路的作用特点，对化疗性肠黏膜炎具有治疗作用，能通过TLR4/NF-κB通路降低化疗性肠黏膜炎模型大鼠炎性水平发挥治疗作用。

Objective To explore the mechanism of Renshen Jianpi Pills in treatment of chemotherapy-induced intestinal mucositis based on network pharmacology and animal experiments vetificatio. Methods Collect the active ingredients and potential therapeutic targets of Renshen Jianpi Pills for chemotherapy-induced intestinal mucositis through an open traditional Chinese medicine database and disease data platform. Construct a PPI network through the STING online analysis platform, and explore the effective ingredients, potential therapeutic targets, and pathways of Renshen Jianpi Pills for chemotherapy-induced intestinal mucositis through GO functional enrichment analysis and KEGG pathway enrichment analysis. The rats were randomly divided into control group, model group, glutamine powder group, and Renshen Jianpi Pills (4.8, 2.4, and 1.2 g/kg) groups, with 12 rats in each group. Samples were taken 24 hours after the last dose. The general state, body weight and diarrhea score of rats were observed. Changes of serum inflammatory factors; Pathological changes of intestinal tissue and TLR/ NF-κB changes. Results Network pharmacology research results: 76 Active ingredients of Renshen Jianpi Pills were selected, among which quercetin, kaempferol, and naringenin have the most corresponding targets, which may be the effective ingredients of Renshen Jianpi Pills. 152 Potential target proteins were collected, and its main target proteins involve MAPK3, Akt1, TNF, IL6, NF-κB. Signaling pathways involve PI3K/Akt signaling pathway, IL-17 signaling pathway, tumor necrosis factor signaling pathway, MAPK signaling pathway, etc. The results of animal experiments showed as follows: Compared with model group, the body mass of rats in Renshen Jianpi Pills 4.8 g/kg group was significantly increased (P < 0.05). The diarrhea scores of rats in the groups of Renshen Jianpi Pills (4.8, 1.2 g/kg) were significantly decreased (P < 0.05, 0.01). The intestinal histopathological scores of rats in the groups of Renshen Jianpi Pills (4.8, 2.4 g/kg) were significantly decreased (P < 0.01). The levels of TNF-α and IL-1β in serum of rats in 4.8 g/kg group were significantly decreased (P < 0.05, 0.01). The serum IL-1β in the 2.4 g/kg group of rats was significantly decreased (P < 0.05). The expressions of TLR4 and NF-κB protein in intestinal tissue of rats in the groups of Panshen Jianpi Pills (4.8, 1.2 g/kg) were significantly decreased (P < 0.05, 0.01). Conclusion Renshen Jianpi Pills has the characteristics of multi-component, multi-target and multi-pathway action. It has the therapeutic effect on chemotherapy-induced intestinal mucositis, and can reduce the inflammatory level of chemotherapy-induced intestinal mucositis model rats through TLR4/NF-κB pathway.

R975

北京市中医药科技发展资金项目(BJZYYB-2023-70)