目的 探究人參皂苷Rb₁（ginsenoside Rb₁，Rb₁）治療大鼠代謝相關(guān)脂肪性肝?。∕AFLD）的作用靶點(diǎn)及機(jī)制。方法 采用網(wǎng)絡(luò)藥理學(xué)方法系統(tǒng)地預(yù)測Rb₁治療MAFLD的核心靶點(diǎn)，通過STRING平臺和Cytoscape3.9.1軟件分別繪制蛋白質(zhì)相互作用（PPI）網(wǎng)絡(luò)圖譜和“Rb₁-MAFLD靶點(diǎn)”網(wǎng)絡(luò)模型，利用DAVID數(shù)據(jù)庫對核心靶點(diǎn)進(jìn)行基因本體（GO）功能富集與京都基因與基因組百科全書（KEGG）通路富集分析。動物體內(nèi)實(shí)驗(yàn)進(jìn)行驗(yàn)證，高脂飼料誘導(dǎo)建立實(shí)驗(yàn)性MAFLD大鼠模型。測定各組大鼠體質(zhì)量、肝臟系數(shù)、肝功能指標(biāo)[天冬氨酸氨基轉(zhuǎn)移酶（AST）、丙氨酸氨基轉(zhuǎn)移酶（ALT）]及血脂指標(biāo)[三酰甘油（TG）、總膽固醇（TC）、低密度脂蛋白膽固醇（LDL-C）、高密度脂蛋白膽固醇（HDL-C）]；HE染色觀察肝組織病理學(xué)變化；酶聯(lián)免疫吸附（ELISA）和實(shí)時(shí)熒光定量聚合酶鏈?zhǔn)椒磻?yīng)（qRT-PCR）法分別檢測大鼠血清和肝臟中炎癥因子[白細(xì)胞介素-6（IL-6）、IL-10、腫瘤壞死因子-α（TNF-α）和轉(zhuǎn)化生長因子-β1（TGF-β1）]表達(dá)水平以驗(yàn)證網(wǎng)絡(luò)藥理學(xué)預(yù)測結(jié)果；16 S rDNA測序分析評估Rb₁對MAFLD大鼠腸道菌群組成的影響。結(jié)果 獲得134個Rb₁治療MAFLD的潛在靶點(diǎn)，富集分析顯示Rb₁干預(yù)MAFLD的生物學(xué)過程與轉(zhuǎn)錄調(diào)控、細(xì)胞增殖、炎癥反應(yīng)等相關(guān)，作用的通路主要為癌癥、炎癥、脂質(zhì)和動脈粥樣硬化、糖尿病等途徑。動物實(shí)驗(yàn)結(jié)果顯示，與對照組相比較，MAFLD模型組大鼠肝臟系數(shù)、肝功能指標(biāo)、炎癥因子水平顯著升高，血脂代謝紊亂，且腸道菌群結(jié)構(gòu)紊亂。Rb₁可改善肝組織中脂肪變性及炎癥細(xì)胞浸潤，顯著降低血清中AST、ALT、TC、TG、LDL-C水平，增加HDL-C水平，且有效抑制MAFLD大鼠中炎癥因子的過表達(dá)；此外，Rb₁改變了MAFLD大鼠的腸道菌群的組成，以擬桿菌門、乳桿菌屬、布勞特氏菌屬富集和脫硫弧菌減少為特征。結(jié)論 Rb₁能通過改善血脂紊亂與肝功能、抑制炎癥反應(yīng)和調(diào)節(jié)腸道菌群的穩(wěn)態(tài)，最終發(fā)揮抗MAFLD的作用。

Objective This study was carried out to investigate the targets and mechanisms of action of ginsenoside Rb₁(Rb₁) in the therapy of metabolic associated fatty liver disease (MAFLD) in rats. Methods The network pharmacology methods were used to systematically predict the core targets of ginsenoside Rb₁ for the treatment of MAFLD. PPI network and "Rb₁-MAFLD targets" networks were plotted using STRING platform and Cytoscape3.9.1 software, respectively. GO functional enrichment and KEGG pathway enrichment analysis were performed on core targets using DAVID database. Further in vivo animal experiments were conducted for validation, an experimental MAFLD model was developed in rats by feeding them high-fat diet. Body mass, liver coefficient, liver function index (AST, ALT) and blood lipid index (TG, TC, LDL-C, HDL-C) were determined. HE staining was used to observe the pathological changes of liver tissue. The expression levels of inflammatory factors (IL-6, IL^-10, TNF-α, TGF-β1) in serum and liver of rats were detected by ELISA and real-time PCR, respectively, to validate the predicted results of network pharmacology. 16S rDNA sequencing analysis was used to evaluate the effect of Rb₁ on gut microbiota composition in MAFLD rats. Results A total of 134 potential targets for Rb₁ treatment of MAFLD were obtained. Enrichment analysis indicated that Rb 1 interferes with the biological process of MAFLD, which is related to transcriptional regulation, cell proliferation and inflammatory response, and the action pathways are mainly cancer, inflammation, lipid and atherosclerosis and diabetes. The results of animal experiments indicated that compared with the normal group, rats in the MAFLD model group had conspicuously elevated liver coefficients, liver function indexes, inflammatory factors, disturbed lipid metabolism, and structural disorders of the intestinal microbiota. Rb 1 improved steatosis and inflammatory cell infiltration in liver tissues, conspicuously reduced serum levels of AST, ALT, TC, TG, and LDL-C, increased HDL-C levels, and effectively suppressed the overexpression of inflammatory factors in MAFLD rats. Furthermore, Rb₁ altered the composition of the gut microbiota in MAFLD rats, characterized by the enrichment of Bacteroidota, Lactobacillus, Blautia and the reduction of Firmicutes/Bacteroidota and Desulfovibrio. Conclusion Rb₁ can ultimately exert anti-MAFLD effects by improving dyslipidemia and liver function, suppressing inflammatory responses and modulating the homeostasis of the gut microbiota.

R285.5

黑龍江省中醫(yī)藥學(xué)會2022—2024年度青年人才托舉工程項(xiàng)目（2022-QNRC1-27）；中醫(yī)藥科研課題和國醫(yī)大師學(xué)術(shù)思想傳承科研課題項(xiàng)目（ZHY2022-115）；黑龍江省自然科學(xué)基金項(xiàng)目（ZD2020H006）