基于斑马鱼模型和网络药理学研究小柴胡汤治疗非酒精性脂肪肝病的作用及潜在机制  

Effect and Potential Mechanism of Xiaochaihu Decoction on Non-alcoholic Fatty Liver Disease Based on Zebrafish Model and Network Pharmacology

作　　者：蒋智锐 李彪平 张靖怡 劳梓滢 徐辉 刘览博 杨加顺 唐玲 JIANG Zhirui;LI Biaoping;ZHANG Jingyi;LAO Ziying;XU Hui;LIU Lanbo;YANG Jiashun;TANG Ling(School of Traditional Chinese Medicine,Southern Medical University,Guangzhou 510515,China;Institute of Intersection and Transformation of Traditional Chinese Medicine,School of Traditional Chinese Medicine,Southern Medical University,Guangzhou 510515,China;Guangdong Provincial Key Laboratory of Traditional Chinese Medicine Preparations/Guangdong Provincial Technical Engineering Laboratory of Traditional Chinese Medicine Preparations,Guangzhou 510515,China;Shenzhen Hospital of Beijing University of Chinese Medicine,Shenzhen 518100,China;The Seventh Affiliated Hospital of Southern Medical University,Foshan 528244,China)

机构地区：[1]南方医科大学中医药学院,广州510515 [2]南方医科大学中医药学院中医药交叉与转化研究所,广州510515 [3]广东省中药制剂重点实验室/广东省中药制剂技术工程实验室,广州510515 [4]北京中医药大学深圳医院,广东深圳518100 [5]南方医科大学第七附属医院,广东佛山528244

出　　处：《中国现代应用药学》2024年第23期3285-3295,共11页Chinese Journal of Modern Applied Pharmacy

基　　金：广东省中医药管理局项目(20211260)。

摘　　要：目的基于斑马鱼模型及网络药理学技术探究小柴胡汤治疗非酒精性脂肪肝病(non-alcoholic fatty liver disease,NAFLD)的活性成分、作用靶点及潜在机制。方法采用高脂高胆固醇饲料喂养诱导斑马鱼幼鱼NAFLD模型,以斑马鱼肝脏表型、HE病理切片和炎症因子表达水平指标,评价小柴胡汤对NAFLD的防治作用,结合网络药理学分析其可能的作用机制。结果与模型组相比,小柴胡汤可剂量依赖性降低NAFLD模型斑马鱼幼鱼的体质量与身体质量指数的增加,缓解肝脏脂肪变性、脂质沉积和结构损伤,降低斑马鱼体内的TG、TC、ALT、AST含量,降低ROS水平并提高SOD酶活力,同时降低炎症因子TNF-α、IL-6、IL-1β的mRNA表达水平。网络药理学得到小柴胡汤药效活性成分198个与作用靶点108个,主要富集于PI3K-Akt信号通路及细胞凋亡相关信号通路,蛋白互作网络分析得到汉黄芩素、6-姜辣素等关键活性成分和PTGS2等核心靶点,高剂量小柴胡汤可以显著调节NAFLD斑马鱼体内上述核心靶点基因的mRNA表达水平。结论小柴胡汤可通过多成分、多途径、多靶点干预NAFLD早期的NAFL-NASH进展,其主要活性成分汉黄芩素等可能通过调节PTGS2、AKT1等靶点,参与调控PI3K-Akt信号通路及细胞凋亡相关信号通路等来发挥降脂、保肝、抗氧化、抗炎的作用。OBJECTIVE To explore the active ingredients,targets,and potential mechanisms of Xiaochaihu Decoction(XCHD)in the treatment of non-alcoholic fatty liver disease(NAFLD)based on the zebrafish model and network pharmacology technology.METHODS The zebrafish NAFLD model was established by feeding zebrafish larvae with high-fat and high-cholesterol diet.The evaluation indicators,including zebrafish liver phenotype,HE pathological slices,and expression levels of inflammatory factors,were used to comprehensively evaluate the effect of XCHD on NAFLD.Network pharmacology analysis was used to explore its potential mechanisms of action.RESULTS Compared with the model group,XCHD could dosedependently reduce the increase of body weight and body mass index of zebrafish larvae model with NAFLD,alleviate liver steatosis,lipid deposition,and structural damage,reduce the levels of TG,TC,ALT,AST in zebrafish,decrease ROS levels,and increase SOD enzyme activity.It also reduced the mRNA expression levels of inflammatory factors TNF-α,IL-6,IL-1βin zebrafish.There were 198 active ingredients and 108 targets of XCHD identified by network pharmacology,mainly enriched in the PI3K-Akt signaling pathway and apoptosis-related signaling pathways.PPI network analysis revealed key active ingredients such as baicalin,6-gingerol,and core targets such as PTGS2.High-dose XCHD significantly regulated the mRNA expression levels of these core targets in NAFLD zebrafish.CONCLUSION XCHD can intervene in the early progression of NAFL to NASH through multiple components,pathways,and targets.Its main active ingredient,baicalin,can exert lipid-lowering,hepatoprotective,antioxidant,and anti-inflammatory effects by modulating targets such as PTGS2 and AKT1,and participating in the regulation of the PI3K-Akt signaling pathway and apoptosis-related signaling pathways.

关 键 词：非酒精性脂肪肝病 小柴胡汤 斑马鱼 网络药理学 

分 类 号：R285.5[医药卫生—中药学]