目的 基于網(wǎng)絡(luò)藥理學(xué)和動物實驗探討人參健脾丸防治化療性腸黏膜炎的有效成分及潛在作用靶點(diǎn)和通路。方法 通過開放的中藥數(shù)據(jù)庫和疾病數(shù)據(jù)平臺收集人參健脾丸的活性成分及治療化療性腸黏膜炎的潛在作用靶點(diǎn)，通過STING在線分析平臺構(gòu)建蛋白相互作用（PPI）網(wǎng)絡(luò)，通過基因本體（GO）功能富集分析和京都基因與基因組百科全書（KEGG）通路富集分析探討人參健脾丸治療化療性腸黏膜炎的有效成分及可能的作用靶點(diǎn)和通路。將大鼠隨機(jī)分為對照組、模型組、谷氨酰胺散組、人參健脾丸（4.8、2.4、1.2 g/kg）組，每組12只。末次給藥后24 h取材。觀察大鼠一般狀態(tài)、體質(zhì)量、腹瀉評分；血清炎性因子的變化情況；腸組織病理改變情況以及Toll樣受體（TLR）/核因子（NF-κB）等的變化情況。結(jié)果 網(wǎng)絡(luò)藥理學(xué)研究結(jié)果顯示，共篩選出人參健脾丸的主要活性成分76個，其中槲皮素、山柰酚和柚皮素對應(yīng)靶點(diǎn)最多，可能是人參健脾丸治療化療性腸黏膜炎的有效成分。其用于腸黏膜炎潛在靶點(diǎn)蛋白152個，主要作用靶點(diǎn)蛋白涉及絲裂原活化蛋白激酶（MAPK）3、蛋白激酶B1（Akt1）、腫瘤壞死因子（TNF）、白細(xì)胞介素（IL）-6、NF-κB等，作用通路涉及磷脂酰肌醇3-激酶（PI3K）/Akt信號通路、IL-17信號通路、腫瘤壞死因子信號通路、MAPK信號通路等。動物實驗結(jié)果顯示：與模型組比較，人參健脾丸4.8 g/kg組大鼠體質(zhì)量顯著升高（P＜0.05）；人參健脾丸（4.8、1.2 g/kg）組大鼠腹瀉評分顯著降低（P＜0.05、0.01）；人參健脾丸（4.8、2.4 g/kg）組大鼠腸組織病理評分顯著降低（P＜0.01）；人參健脾丸4.8 g/kg組大鼠血清中TNF-α和IL-1β水平均顯著降低（P＜0.05、0.01）；人參健脾丸2.4 g/kg組大鼠血清中IL-1β顯著降低（P＜0.05）；人參健脾丸（4.8、1.2 g/kg）組大鼠腸組織TLR4、NF-κB蛋白表達(dá)顯著降低（P＜0.05、0.01）。結(jié)論 人參健脾丸具有多成分、多靶點(diǎn)、多通路的作用特點(diǎn)，對化療性腸黏膜炎具有治療作用，能通過TLR4/NF-κB通路降低化療性腸黏膜炎模型大鼠炎性水平發(fā)揮治療作用。

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

北京市中醫(yī)藥科技發(fā)展資金項目(BJZYYB-2023-70)