目的 通過網(wǎng)絡(luò)藥理學(xué)、分子對(duì)接及動(dòng)物實(shí)驗(yàn)探討沙棘對(duì)肝臟脂質(zhì)蓄積的作用機(jī)制。方法 中藥系統(tǒng)藥理學(xué)數(shù)據(jù)庫與分析平臺(tái)（TCMSP）、Swiss Target Prediction數(shù)據(jù)庫篩選沙棘的活性成分和靶點(diǎn)，Gene Cards及OMIM數(shù)據(jù)庫獲取代謝相關(guān)脂肪性肝?。∕AFLD）相關(guān)疾病靶點(diǎn)，Cytoscape構(gòu)建“藥物-成分-靶點(diǎn)”網(wǎng)絡(luò)。蛋白質(zhì)-蛋白質(zhì)相互作用（PPI）網(wǎng)絡(luò)分析識(shí)別關(guān)鍵靶點(diǎn)，對(duì)核心靶點(diǎn)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，將主要成分和靶點(diǎn)進(jìn)行分子對(duì)接。24只ApoE^-/-小鼠分為對(duì)照組、模型組和沙棘低、高劑量（100、200 mg·kg^-1）組。對(duì)照組飼喂普通飼料，其他組飼喂高脂飼料16周，沙棘組ig給藥16周。檢測(cè)小鼠血脂水平，蘇木精-伊紅（HE）染色檢測(cè)肝臟病理形態(tài)，油紅O染色檢測(cè)肝臟脂質(zhì)蓄積，測(cè)定肝臟脂質(zhì)總膽固醇（TC）、三酰甘油（TG）水平，蛋白質(zhì)印跡法（Western blotting）檢測(cè)過氧化物酶體增殖物激活受體γ（PPARγ）、沉默調(diào)節(jié)蛋白1（SIRT1）、磷脂酰肌醇3-激酶/蛋白激酶B（PI3K-Akt）相關(guān)蛋白表達(dá)。結(jié)果 篩選沙棘活性成分33種，作用靶點(diǎn)345個(gè)，MAFLD相關(guān)靶點(diǎn)1 832個(gè)，共同靶點(diǎn)120個(gè)，核心靶點(diǎn)為雌激素受體1（ESR1）、絲氨酸/蘇氨酸蛋白激酶1（Akt1）、PPARG、SIRT1等，主要通過調(diào)控PI3K-Akt信號(hào)通路等，分子對(duì)接表明主要成分與關(guān)鍵靶點(diǎn)結(jié)合活性良好。動(dòng)物實(shí)驗(yàn)結(jié)果表明，沙棘可降低TC、TG及低密度脂蛋白膽固醇（LDL-C）水平，升高高密度脂蛋白膽固醇（HDL-C）水平，減少肝臟脂肪變性及脂質(zhì)蓄積，降低肝臟TC、TG水平，升高PPARγ、SIRT1及p-PI3K、p-Akt蛋白表達(dá)。結(jié)論 沙棘調(diào)節(jié)血脂，減少肝臟脂質(zhì)蓄積，其機(jī)制可能與激活PPARγ/SIRT1和PI3K/Akt信號(hào)通路相關(guān)。

Objective To explore the mechanism of Hippophae Fructus on metabolic dysfunction-associated fatty liver disease (MAFLD) through network pharmacology, molecular docking and animal experiments. Methods The active components and targets of Hippophae Fructus were screened by TCMSPS and Swiss Target Prediction databases, and the disease targets related to MAFLD were obtained from Gene Cards and OMIM databases. The "drug-component-target" network was constructed by Cytoscape. The key targets were identified by PPI network analysis, and GO and KEGG pathway enrichment analysis were performed on the core targets. Molecular docking was conducted on the main components and targets. Total of 24 ApoE^-/- mice were divided into control group, model group, low- and high-dose (100 and 200 mg·kg^-1) Hippophae Fructus group. The control group was fed with normal diet, and the other groups were fed with high-fat diet for 16 weeks. The Hippophae Fructus groups were given intragastric administration for 16 weeks. The blood lipid levels of mice were detected, and the liver pathological morphology was detected by HE staining. The liver lipid accumulation was detected by Oil Red O staining, and the levels of TC and TG in the liver were determined. The expressions of PPARγ, SIRT1, and PI3K/AKT-related proteins were detected by Western blotting. Results A total of 33 active components and 345 targets of Hippophae Fructus were screened, 1 832 MAFLD-related targets were obtained, and 120 common targets were identified. The core targets were ESR1, AKT1, PPARG, SIRT1, etc. The main mechanism was through the PI3K-Akt signaling pathway, and the molecular docking showed that the main components had good binding activity with the key targets. The animal experiment results showed that Hippophae Fructus reduced serum TC, TG and LDL-C levels (P < 0.01), increased HDL-C levels (P < 0.05), reduced liver steatosis and lipid accumulation, decreased liver TC and TG levels (P < 0.05, 0.01), increased PPARγ, SIRT1, p-PI3K and p-Akt protein expression (P < 0.01). Conclusion Hippophae Fructus reduces blood lipids and liver lipid accumulation, and its mechanism may be related to the activation of PPARγ/SIRT1 and PI3K/AKT signaling pathway.

R285.5

國家自然科學(xué)基金項(xiàng)目（82374077）；陜西省中醫(yī)藥科研創(chuàng)新人才項(xiàng)目（TZKN-CXRC-02）；咸陽市科技創(chuàng)新人才項(xiàng)目（L2024-CXNL-KJRCTD-KJRC-0003）；秦創(chuàng)原中醫(yī)藥產(chǎn)業(yè)創(chuàng)新聚集區(qū)項(xiàng)目（L2024-QCY-ZYYJJQ-X45）；大學(xué)生創(chuàng)新創(chuàng)業(yè)訓(xùn)練計(jì)劃項(xiàng)目（202310716075）