| 引用本文: |
廖小妹,陈美丽,王玺舜,唐博翔,何文智.加味消脂利肝方治疗非酒精性脂肪肝的网络药理学研究及实验验证[J].湖南中医药大学学报,2023,43(2):317-326[点击复制] |
|
| |
|
|
| 本文已被：浏览 1110次 下载 390次 |
| 加味消脂利肝方治疗非酒精性脂肪肝的网络药理学研究及实验验证 |
| 廖小妹,陈美丽,王玺舜,唐博翔,何文智 |
| (湖南中医药大学口腔医学院, 湖南 长沙 410208;湖南中医药大学, 湖南 长沙 410208;湖南中医药大学附属长沙市中医医院, 湖南 长沙 410002) |
| 摘要: |
| 目的 基于网络药理学预测加味消脂利肝方治疗非酒精性脂肪肝（non-alcoholic fatty liver disease, NAFLD）的作用机制，并通过实验验证加味消脂利肝方治疗NAFLD的作用。方法 通过TCMSP收集加味消脂利肝方的主要化学成分及靶点信息；使用GeneCards和OMIM数据库获取NAFLD相关靶点；通过STRING平台对药物疾病靶蛋白进行蛋白质-蛋白质相互作用（protein-protein interaction, PPI）网络构建，运用Cytoscape 3.9.0对PPI图进行关键靶点分析；利用Metascape数据库对共有靶点进行基因本体（gene ontology, GO）、京都基因与基因组百科全书（Kyoto encyclopedia of genes and genomes, KEGG）数据库通路富集分析。实验验证利用高脂饮食诱导法（high-fat feed, HFD）构建NAFLD大鼠模型，分为空白组，模型组，加味消脂利肝方低、中、高剂量组，阳性药组。灌胃2周后，HE染色观察各组血清、肝组织的形态学。结果 通过网络药理学预测得到加味消脂利肝方通过IL-6、TNF、JUN、IL-1ß、CXCL8等核心靶点发挥抗炎消脂作用，KEGG富集到基因通路198条，其中包括PI3K/Akt信号通路、TNF信号通路等。验证实验表明，与空白组相比，模型组ALT、AST、TG、TC、LDL-C血清浓度明显升高（P<0.05或P<0.01），HDL-C血清浓度明显降低（P<0.01），脂滴区域增加。与模型组相比，加味消脂利肝方组NAFLD大鼠血清ALT、AST、TG、TC、LDL-C水平降低（P<0.05），HDL-C水平升高（P<0.05），脂滴区域减少。结论 加味消脂利肝方具有多通路、多靶点的优势，能改善血清脂质水平及肝功能，减少肝脏内脂质沉积，最终发挥治疗NAFLD的作用。 |
| 关键词: 加味消脂利肝方 非酒精性脂肪肝 脂质水平 实验验证 网络药理学 |
| DOI：10.3969/j.issn.1674-070X.2023.02.023 |
| 投稿时间：2022-10-20 |
| 基金项目:湖南省卫生健康委员会（D202308018795）；湖南中医药大学创新项目（2021YF08，2021dj04）。 |
|
| Network pharmacology analysis and experimental verification of Jiawei Xiaozhi Ligan Decoction in treating NAFLD |
| LIAO Xiaomei,CHEN Meili,WANG Xishun,TANG Boxiang,HE Wenzhi |
| (Stomatological College, Hunan University of Chinese Medicine, Changsha, Hunan 410208, China;Hunan University of Chinese Medicine, Changsha, Hunan 410208, China;Changsha Hospital of Chinese Medicine in Hunan University of Chinese Medicine, Changsha, Hunan 410002, China) |
| Abstract: |
| Objective To identify the mechanism of Jiawei Xiaozhi Ligan Decoction (JWXZLGD) in treating non-alcoholic fatty liver disease (NAFLD) based on network pharmacology, and to verify the effects on NAFLD by experiments. Methods TCMSP database was used to screen the active compounds of JWXZLGD and the target sites. Meanwhile, GeneCards and the OMIM database were applied to obtain NAFLD related targets. Protein-protein interaction (PPI) network of the disease target proteins was constructed with the String platform and the key targets in PPI maps were then analyzed by Cytoscape 3.9.0. Then enrichment pathway analysis of GO and KEEG was done based on the Metascape database. Molecular docking of key targets is also performed with the iGemdock Molecular Docking Tool. Finally, experimental verification was carried out by high-fat feed (HFD) to construct a rat model of NAFLD, which was divided into blank group, model group, low-, medium-, high-dose Jiawei Xiaozhi Ligan Decoction group and positive drug group. After 2 weeks of gastric irrigation, morphological observation was carried out on the HE stained liver tissue of serum in each group. Results Based on network pharmacology, JWXZLGD could take anti-inflammatroy and fat lowering effects by core targets such as IL-6, TNF, JUN, IL-1β, and CXCL8, and KEGG is enriched to 198 gene pathways, including NF-κB, PI3K/Akt, TNF, and other signaling pathways. Compared with the blank group, the model group showed the significantly higher serum concentrations of ALT, AST, TG, TC, and LDL-C (P<0.05 or P<0.01), and the significantly lower serum concentration of HDL-C (P<0.01), and demonstrated an increase in lipid droplet area. Compared with the model group, the JWXZLGD group demonstrated lower serum ALT, AST, TG, TC, and LDL-C (P<0.05), higher HDL-C levels (P<0.05) and a decrease in the area of lipid droplets. Conclusion JWXZLGD has multiple pathways and targets, which can improve serum lipid levels and liver function, reduce lipid deposition in the liver, and ultimately play a role in the treatment of NAFLD. |
| Key words: Jiawei Xiaozhi Ligan Decoction non-alcoholic fatty liver disease lipid level experimental verification network pharmacology |
|
二维码（扫一下试试看！） |
|
|
|
|
