摘要
目的基于网络药理学和非酒精性脂肪肝病(NAFLD)动物模型实验,挖掘并验证制何首乌治疗NAFLD的作用机制。方法查阅文献比较何首乌及制何首乌药物成分的不同;通过HERB数据库及SwissADME查找筛选制何首乌药效成分,Swiss Target Prediction预测靶点,OMIM、DISGENET、GEENCARDS数据库筛选NAFLD相关靶点,药效成分靶点与疾病靶点互相映射,使用DAVIDV6.8进行GO功能富集分析和KEGG通路富集分析,Cytoscape3.7.2绘制制何首乌治疗NALFD“成分-靶点-KEGG信号通路-疾病”网络;NAFLD小鼠行制何首乌灌胃治疗8周,检测血清甘油三酯含量及谷丙转氨酶活性;HE染色观察小鼠肝组织病变;Western blot实验对制何首乌治疗NAFLD的潜在作用机制进行验证。结果通过网络药理学筛选出了6种制何首乌治疗NAFLD的药效成分及32个潜在作用靶点,GO和KEGG通路富集到脂质和动脉硬化相关通路、AMPK信号通路等;与NALFD小鼠相比,药物干预组小鼠血清甘油三酯、谷丙转氨酶活性下降;HE染色验证制何首乌具有改善NAFLD的功能,且Western blot显示制何首乌干预后AMPK信号通路的脂肪酸合成酶(Fatty acid synthase,FASN),乙酰辅酶A羧化酶(Acetyl CoA carboxylase,ACC)及硬脂酰辅酶A去饱和酶1(Stearoyl-CoA desaturase 1,SCD1)蛋白表达量相关。结论制何首乌可能通过调控AMPK信号通路相关蛋白FASN、ACC、SCD1表达,减少肝脂质新生,缓解NAFLD肝脂滴蓄积。
Objective To explore and validate the mechanism of Prepared Radix Polygoni Multiflori in the treatment of NAFLD based on network pharmacology and animal non-alcoholic fatty liver disease(NAFLD)model experiments.Methods Consult the literature to compare the differences between Radix Polygoni Multiflori and Prepared Radix Polygoni Multiflori(PRPM).Herb database and SwissADME database were used to screen the active ingredients of Prepared Radix Polygoni Multiflori,SwissTargetPrediction database was used to predict its targets,OMIM,DISGENET and GEENCARDS databases were used to screen the NAFLD-related targets,conduct GO functional enrichment analysis and KEGG pathway enrichment analysis.The active ingredient-target-KEGG signaling pathway-NAFLD network was mapped later.The mice with NAFLD were treated with Prepared Radix Polygoni Multiflori by gavage for 8 weeks;serum triglyceride level and alanine aminotransferase(ALT)activity were measured;the liver lesions were observed by HE staining;the potential mechanism of action of Radix Polygoni Multiflori in the treatment of NAFLD was verified by Western blot.Results The differences between Radix Polygoni Multiflori and PRPM were consulted.Six pharmacological components and 32 potential action targets of Radix Polygoni Multiflori for the treatment of NAFLD were screened by network pharmacology,GO and KEGG pathways were enriched to lipid and atherosclerosis-related pathways,AMPK signaling pathway,etc.;HE staining verified that Prepared Radix Polygoni Multiflori has the function of improving NAFLD and is associated with the alteration of FASN,ACC,SCD protein of AMPK signaling pathway.Conclusion Radix Polygoni Multiflori has the potential to improve NAFLD by regulating FASN,ACC and SCD.
作者
杨慧茹
黄昶煜东
朱丽英
李程程
许永劼
李兴
潘卫
张祖隆
Yang Huiru;Huang Changyudong;Zhu Liying;Li Chengcheng;Xu Yongjie;Li Xing;Pan Wei;Zhang Zulong(Affiliated Hospital of Guizhou Medical University,Guiyang 550004,China;School of Basic Medicine,Guizhou University of Traditional Chinese Medicine,Guiyang 550025,China)
出处
《世界科学技术-中医药现代化》
CSCD
北大核心
2023年第11期3678-3691,共14页
Modernization of Traditional Chinese Medicine and Materia Medica-World Science and Technology
基金
国家自然科学基金委员会地区科学基金(81960822):基于代谢组学的制何首乌防治糖尿病脑病的药效成分和作用机制的研究,负责人:李兴
贵州省科学技术厅贵州省科技计划项目(课题)(黔科合基础-ZK[2021]一般366):基于PI3K/AKT/mTOR信号通路探讨IRX5在NAFLD脂肪酸代谢中的调控机制及大黄素干预作用的研究,负责人:李程程
贵州省科学技术厅贵州省科技计划项目(课题)(黔科合基础-ZK[2021]一般483):血清IRX5在肝细胞癌中的临床应用价值研究,负责人:朱丽英
关键词
制何首乌
非酒精性脂肪肝病
网络药理学
脂肪酸合成酶
Radix Polygoni Multiflori
Nonalcoholic fatty liver disease
Network pharmacology
Fatty acid synthase
作者简介
通讯作者:张祖隆,硕士研究生导师,主要研究方向:肾脏病、血液净化及糖尿病肾病。
