目的 探討四磨湯在膿毒癥治療中的潛在機制，并通過動物實驗、網(wǎng)絡(luò)藥理學(xué)和分子對接技術(shù)揭示其活性成分及作用靶點。方法 50只小鼠隨機分為5組：四磨湯高、中、低劑量（12.00、7.56、3.00 mL·kg⁻¹）組、模型組以及對照組，除對照組外，采用ip注射25 mg·kg⁻¹脂多糖制作BALB/c小鼠膿毒癥模型。記錄造模后24 h各組小鼠死亡率以及檢測血清中白細(xì)胞介素-1β（IL-1β）、IL-6、腫瘤壞死因子-α（TNF-α）水平。利用中藥系統(tǒng)藥理學(xué)數(shù)據(jù)庫與分析平臺（TCMSP）篩選四磨湯的活性成分，并通過PubChem數(shù)據(jù)庫獲取其小分子結(jié)構(gòu)。采用SwissTargetPrediction預(yù)測潛在靶點，利用GeneCards和CTD數(shù)據(jù)庫篩選膿毒癥相關(guān)靶點。通過R語言“VennDiagram”包分析四磨湯靶點與膿毒癥靶點的交集，并進(jìn)行基因本體（GO）注釋及京都基因與基因組百科全書（KEGG）通路富集分析。采用STRING數(shù)據(jù)庫和Cytoscape3.10.2軟件確定核心靶點，利用AutoDock4.2.6軟件進(jìn)行分子對接分析。結(jié)果 造模后24 h，四磨湯治療后明顯降低膿毒癥小鼠的死亡率，以及明顯抑制炎癥因子的表達(dá)，差異具有統(tǒng)計學(xué)意義（P＜0.05）。篩選出四磨湯中的26個活性成分，識別出737個靶點，與膿毒癥相關(guān)的3 240個靶點交集得到325個潛在靶點。GO和KEGG分析顯示，四磨湯的靶點主要涉及炎癥反應(yīng)、免疫調(diào)節(jié)和組織修復(fù)通路。其重要活性成分為lappadilactone，核心靶點包括絲氨酸和蘇氨酸激酶1（AKT1）、非受體酪氨酸蛋白激酶（SRC）和表皮生長因子受體（EGFR），分子對接結(jié)果表明lappadilactone與這些靶點具有良好的結(jié)合能力，結(jié)合能分別−29.33、−24.73、−17.36 kJ·mol⁻¹。動物實驗顯示四磨湯可以降低膿毒癥小鼠血清中AKT1水平，差異具有統(tǒng)計學(xué)意義（P＜0.05）。結(jié)論 四磨湯通過調(diào)節(jié)AKT1、SRC和EGFR等核心靶點，可能對膿毒癥產(chǎn)生治療作用。

Objective To investigate the potential mechanisms of Simo Decoction in the treatment of sepsis and elucidate its active components and therapeutic targets through animal experiments, network pharmacology, and molecular docking techniques. Methods A sepsis model was established in BALB/c mice by ip injection of lipopolysaccharide (25 mg·kg⁻¹). Fifty mice were randomly divided into five groups: Simo Decoction high-, middle-, low-dose (12.00, 7.56, 3.00 mL·kg⁻¹) groups, model group, and control group. Mortality rates were recorded 24 h after modeling, and serum levels of IL-1β, IL-6, and TNF-α were measured. Active components of Simo Decoction were identified using the Traditional Chinese Medicine Systems Pharmacology Database (TCMSP), and their molecular structures were retrieved from the PubChem database. Potential targets were predicted using SwissTargetPrediction, and sepsis-related targets were identified through the GeneCards and Comparative Toxicogenomics Database (CTD). The intersection of Simo Decoction targets and sepsis targets was analyzed using the "VennDiagram" package in R. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted. Core targets were identified through the STRING database and Cytoscape 3.10.2 software. Molecular docking analyses were performed using AutoDock 4.2.6. Results At 24 h post-modeling, Simo Decoction treatment significantly reduced mortality and inhibited the expression of inflammatory cytokines in septic mice, with statistically significant differences (P < 0.05). Twenty-six active components of Simo Decoction were identified, yielding 737 potential targets. The intersection with 3 240 sepsis-related targets resulted in 325 common targets. GO and KEGG analyses revealed that Simo Decoction primarily targets pathways associated with inflammation, immune regulation, and tissue repair. The key active component, lappadilactone, was found to interact with core targets AKT1, SRC, and EGFR. Molecular docking demonstrated favorable binding energies of lappadilactone with these targets, at −29.33, −24.73, −17.36 kJ·mol⁻¹, respectively. Animal experiments demonstrated that Simo Decoction significantly reduced serum AKT1 levels in septic mice, with the difference being statistically significant (P < 0.05). Conclusion Simo Decoction may exert therapeutic effects on sepsis by targeting key molecules such as AKT1, SRC, and EGFR. These findings provide theoretical support for the application of Simo Decoction in sepsis treatment, although further studies are required to verify its clinical efficacy and safety.

R285.5