目的 基于磷脂酰肌醇3激酶（PI3K）/蛋白激酶B（Akt）通路探讨铁皮石斛防治代谢相关性脂肪性肝病的作用机制。方法 在中国知网和PubMed数据库中筛选铁皮石斛主要活性成分，并通过Swiss Target Prediction平台获取活性成分的潜在作用靶点。从GeneCards、OMIM、TTD数据库收集代谢相关性脂肪性肝病的相关靶点，通过韦恩图获取交集靶点。运用Cytoscape 3.10.1软件构建“铁皮石斛–活性成分–靶点–代谢相关性脂肪性肝病”网络，并利用STRING数据库构建蛋白质相互作用（PPI）网络。通过DAVID数据库对交集靶点进行基因本体（GO）和京都基因与基因组百科全书（KEGG）富集分析，并利用Auto Dock Tools软件进行分子对接验证。通过高脂饮食诱导代谢相关性脂肪性肝病大鼠模型，将30只雄性SD大鼠随机均分为对照组、模型组、非诺贝特组及铁皮石斛低、高剂量（500、1 000 mg/(kg·d)）组，每组6只。给药10周后，采用生化试剂盒检测各组大鼠血清及肝脏组织中总胆固醇（TC）、三酰甘油（TG）、高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）水平及血清中丙氨酸氨基转移酶（ALT）、天门冬氨酸氨基转移酶（AST）、白蛋白（ALB）水平；通过苏木精–伊红（HE）和油红O染色观察肝组织病理变化；采用ELISA试剂盒检测血清中白细胞介素-6（IL-6）、IL-1β及肿瘤坏死因子-α（TNF-α）水平；采用实时荧光定量PCR法（RT-qPCR）检测肝组织PI3K、Akt、哺乳动物雷帕霉素靶蛋白（mTOR）、固醇调节元件结合蛋白1（SREBP-1）mRNA表达水平。结果 网络药理学预测得到铁皮石斛的116个活性成分及TNF、ALB、丝氨酸/苏氨酸蛋白激酶1（Akt1）、细胞肿瘤抗原p53（TP53）、过氧化物酶体增殖物激活受体γ（PPARG）等10个核心靶点，提示PI3K/Akt通路可能起关键作用。动物实验表明，与模型组相比，铁皮石斛能显著降低血清TC、TG、LDL-C、ALT、AST及炎症因子水平，提升HDL-C和ALB（P＜0.05），并有效改善肝脏脂肪变性和损伤。RT-qPCR验证铁皮石斛可显著上调肝组织PI3K、Akt mRNA表达，同时抑制下游mTOR、SREBP-1 mRNA的转录（P＜0.05）。结论 铁皮石斛可能通过激活PI3K/Akt信号通路，抑制下游脂质合成相关因子，在高脂饮食诱导的代谢相关性脂肪性肝病模型中发挥了减轻肝脏脂质沉积与炎症反应的有益作用。

Objective To investigate the mechanism of Dendrobium officinale in preventing and treating metabolic-associated fatty liver disease via the phosphatidylinositol 3‑kinase (PI3K)/protein kinase B (Akt) pathway. Methods The main active components of Dendrobium officinale were screened from the CNKI and PubMed databases, and the potential targets of the active components were obtained using the Swiss Target Prediction platform. The targets related to metabolic-associated fatty liver disease were collected from the GeneCards, OMIM, and TTD databases, and the intersecting targets were identified by Venn diagram. Cytoscape 3.10.1 was used to construct the “Dendrobium officinale-active components-targets- metabolic-associated fatty liver disease” network, and the STRING database was applied to establish the protein-protein interaction (PPI) network. The intersecting targets were subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses via the DAVID database, and molecular docking verification was performed using AutoDock Tools. A rat model of metabolic-associated fatty liver disease was induced by a high-fat diet. Thirty male Sprague-Dawley (SD) rats were randomly divided equally into control group, model group, fenofibrate group, and low- and high-dose Dendrobium officinale groups (500 and 1000 mg/(kg·d)), with 6 rats in each group. After 10 weeks of administration, biochemical kits were used to detect the levels of total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) in serum and liver tissues, as well as the serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and albumin (ALB). Hepatic histopathological changes were observed by hematoxylin-eosin (HE) and Oil Red O staining. The serum levels of interleukin-6 (IL-6), IL-1β, and tumor necrosis factor-α (TNF-α) were determined using ELISA kits. The mRNA expression levels of PI3K, Akt, mammalian target of rapamycin (mTOR), and sterol regulatory element-binding protein 1 (SREBP-1) in liver tissues were measured by quantitative real-time polymerase chain reaction (RT-qPCR). Results Network pharmacology prediction identified 116 active components of Dendrobium officinale and 10 core targets, including TNF, ALB, serine/threonine-protein kinase 1 (AKT1), cellular tumor antigen p53 (TP53), and peroxisome proliferator-activated receptor gamma (PPARG), suggesting that the PI3K/Akt signaling pathway may play a key role. Animal experiments showed that compared with the model group, Dendrobium officinale significantly reduced serum levels of TC, TG, LDL-C, ALT, AST and inflammatory factors, and increased HDL-C and ALB levels (P  <  0.05), while effectively ameliorating hepatic steatosis and injury. RT‑qPCR verification confirmed that Dendrobium officinale significantly upregulated PI3K and Akt mRNA in liver tissues, and inhibited the transcription of downstream mTOR and SREBP‑1 mRNA (P  <  0.05). Conclusion Dendrobium officinale may alleviate hepatic lipid accumulation and inflammatory response in high-fat diet-induced metabolic-associated fatty liver disease by activating the PI3K/Akt signaling pathway and inhibiting downstream lipid synthesis-related factors.

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云南省基础研究重点项目（202501AS070136）；云南省科技厅联合专项重点项目（202101AZ07001-008）；云南省傣医药与彝医药重点实验室开放课题项目（2024SS24062）；云南省中西医结合慢病防治重点实验室开放课题项目（YPKLG2024-023）