目的 基于網(wǎng)絡(luò)藥理學(xué)、分子對接及體內(nèi)實驗方法探討霍山石斛對肝損傷的治療作用及其機制。方法 運用中國學(xué)術(shù)期刊全文數(shù)據(jù)庫（CNKI）、PubChem等數(shù)據(jù)庫獲取霍山石斛成分，通過 GeneCards數(shù)據(jù)庫篩選肝損傷相關(guān)基因，將成分靶點與疾病基因交集后構(gòu)建蛋白質(zhì)-蛋白質(zhì)相互作用（PPI）網(wǎng)絡(luò)圖，進(jìn)行基因本體（GO）富集分析和京都基因與基因組百科全書（KEGG）通路富集分析，Cytoscape構(gòu)建“藥物-化合物-靶點”網(wǎng)絡(luò)圖，利用 AutoDock Tools對關(guān)鍵活性成分和核心靶點進(jìn)行分子對接。構(gòu)建乙醇誘導(dǎo)的肝損傷小鼠模型，通過觀察肝臟病理學(xué)改變，試劑盒法測定血清中天冬氨酸氨基轉(zhuǎn)移酶（AST）、丙氨酸氨基轉(zhuǎn)移酶（ALT）及白細(xì)胞介素-6（IL-6）、腫瘤壞死因子-α（TNF-α）水平，通過實時熒光定量逆轉(zhuǎn)錄PCR（qRT-PCR）檢測酒精性肝損傷小鼠肝臟中相關(guān)基因的表達(dá)，考察霍山石斛對酒精性肝損傷小鼠的影響。結(jié)果 篩選出霍山石斛中 33個活性成分，與肝損傷共有靶點 224個，包含 AKT1、EGFR、SRC等，涉及癌癥途徑、PI3K/Akt通路等。體內(nèi)實驗結(jié)果顯示，霍山石斛水提物能夠緩解小鼠酒精性肝損傷，并極顯著降低AST、ALT和TNF-α、IL-6水平（P＜0.01），極顯著下調(diào)IκB激酶（IKK）、核因子-κB（NF-κB）、蛋白激酶B（Akt）mRNA表達(dá)水平（P＜0.01）。結(jié)論 網(wǎng)絡(luò)藥理學(xué)分析及動物實驗結(jié)果，初步證明霍山石斛水提物可以通過下調(diào)Akt、IKK、NF-κB mRNA表達(dá)水平，影響NF-κB信號通路上游，參與酒精性肝損傷通路中炎癥反應(yīng)的調(diào)控，提示霍山石斛具有改善酒精性肝病的潛在作用，為揭示霍山石斛治療肝損傷作用機制提供參考。

Objective To explore the efficacy and mechanism of action of Dendrobium huoshanense in treating liver injury using network pharmacology, molecular docking, and in vivo experiments.Methods China National Knowledge Infrastructure (CNKI), PubChem, and other databases were utilized to identify the components of D. huoshanense. Treatment-related genes for liver injury were selected through the GeneCards databases. After intersecting the component targets with disease genes, a protein-protein interaction (PPI) network was constructed. Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was performed. A "Drug-Compound-Target" network was established using Cytoscape, and key active components and core targets were docked using AutoDock Tools. An ethanol-induced liver injury mouse model was developed. Liver pathology sections were observed, and levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), interleukin-6 (IL-6), and tumor necrosis factor- α (TNF- α) in serum were measured. The expression of related genes in the liver of alcoholic liver injury mice treated with an aqueous extract of D. huoshanense was detected through realtime fluorescence quantitative reverse transcription PCR (qRT-PCR) to assess the impact on alcoholic liver injury mice mice.Results A total of 33 active components were identified in D. huoshanense, correlating with 224 common targets for liver injury, including Akt, EGFR, SRC, and others, involving pathways like cancer and the PI3K/Akt pathway. In vivo experiments showed that the aqueous extract of D. huoshanense could alleviate liver injury in alcoholic liver injury mice. It significantly reduced levels of ALT, AST, TNF-α, and IL-6 (P < 0.01) and markedly downregulated the expression of IκB kinase (IKK), nuclear factor-κB (NF-κB) and protein kinase B (Akt) (P < 0.01).Conclusion Network pharmacology analysis and animal experimental results preliminary demonstrate that the aqueous extract of D. huoshanense can modulate the inflammatory response in the alcohol liver disease pathways by downregulating the expression levels of Akt, IKK, and NF-κB (P < 0.01), thus improving ethanol-induced liver injury. It is suggested that D. huoshanense has the potential effect of improving alcoholic liver disease and provides a reference for revealing the mechanism of D. huoshanense in treating liver injury.

R285.5

國家十四五重點研發(fā)計劃項目（2023YFC3503804）；安徽省科技重大專項（202103b06020004）；安徽省大別山中醫(yī)藥研究院開放課題重點科技攻關(guān)項目（TCMADM-2023-02，TCMADM-2023-08）；安徽省中藥生態(tài)農(nóng)業(yè)工程研究中心開放課題（WXZR202316）；皖西學(xué)院高層次人才基金項目（WGKQ2021083，WGKQ2022074）；國家級、安徽省大學(xué)生創(chuàng)新創(chuàng)業(yè)訓(xùn)練項目（202310376037，s202310376123）；安徽省中藥資源保護(hù)與持續(xù)利用工程實驗室開放課題（TCMRPSU-2022-01）