加味逍遥散治疗肝癌并发抑郁症模型大鼠的网络药理学及蛋白质组学分析  

Network pharmacology and proteomics analysis of Jiawei Xiaoyao San in the treatment of liver cancer complicated with depression in rats

作　　者：温小雨 孙玉浩 李卓娴 徐丽静 夏猛 Wen Xiaoyu;Sun Yuhao;Li Zhuoxian;Xu Lijing;Xia Meng(Basic Medical School,Guangxi University of Chinese Medicine,Nanning 530000,Guangxi Zhuang Autonomous Region,China)

机构地区：[1]广西中医药大学广西中医药大学基础医学院,广西壮族自治区南宁市530000

出　　处：《中国组织工程研究》2022年第32期5132-5142,共11页Chinese Journal of Tissue Engineering Research

基　　金：国家自然科学基金地区基金项目(81860805),项目负责人:夏猛;广西中医药大学2020年自治区级-硕士研究生科研创新项目(YCSW2020191),项目负责人:温小雨;广西中医药大学一流学科建设开放课题(2019XK05),项目负责人:夏猛;广西中医药大学一流学科建设项目重点课题(2018XK010),项目负责人:夏猛。

摘　　要：背景:课题组前期研究表明,加味逍遥散具有调节肝癌并发抑郁大鼠海马中多巴胺、五羟色胺含量的作用,同时能明显改善肝脏病理形态,改善大鼠的抑郁症候,但其药理机制尚未完全阐明。目的:通过全面而整体的蛋白质组学及网络药理学技术筛选出加味逍遥散治疗肝癌并发抑郁模型大鼠的有效靶点,探讨加味逍遥散治疗肝癌并发抑郁症的活性成分及可能的作用机制。方法:构建肝癌并发抑郁症SD大鼠模型,行加味逍遥散干预治疗,对血清中的差异蛋白进行蛋白质组学与网络药理学预测靶点相互印证,对有效靶点进行基因本体论GO富集分析和KEGG富集分析;苏木精-伊红染色检测大鼠肝脏形态、行为学研究观察大鼠抑郁样行为的改变,酶联免疫吸附法测定相关靶点血清中的含量。结果与结论:①蛋白质组学及网络药理学获得3个可能共同蛋白靶点,分别为谷胱甘肽S转移酶μ重组蛋白(glutathione transferase,GSTM1)、3磷酸肌醇依赖性蛋白激酶1(3-phosphoinositide dependent protein kinase1,PDK1)、热休克蛋白90AB1(heat shock protein HSP 90-beta,HSP90AB1),GO富集分析与KEGG通路分析发现其直接参与神经元凋亡过程的负调控、同时涉及PI3K-Akt信号通路和前列腺癌分子信号通路。②苏木精-伊红染色和行为学检测表明加味逍遥散改善了大鼠肝脏损伤及抑郁样行为;酶联免疫吸附检测发现GSTM1、PDK1、HSP90AB1分别在加味逍遥散干预后具有纠正效果。③提示:加味逍遥散可能是通过影响GSTM1、PDK1、HSP90AB1表达纠正大鼠抑郁样行为,改善肝脏形态等作用发挥治疗肝癌并发抑郁症的作用。BACKGROUND:Previous research has shown that Jiowei Xiaoyao San can regulate the content of dopamine and 5-hydroxytryptamine in the hippocampus and significantly improve the pathological morphology of the liver and depression symptoms in rats with liver cancer complicated with depression.Howeve r,its pharmacological mechanism has not been fully elucidated.OBJECTIVE:Through network pharmacological analysis and proteomic testing,to screen out the effective targets of Jio wei Xiaoyao San for treating liver cancer complicated with depression and to discuss the active components and possible mechanism of JiaweiXiaoyao Son in the treatment of liver cancer complicated with depression.METHODS:Sprague-Dawley rat models of liver cancer complicated with depression were established and treated with Jiawei Xiaoyao San.Proteomics and network pharmacology analyses were performed to identify the targets for differentially expressed proteins in serum.Gene ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes enrichment analysis were conducted for effective targets.Liver morphology was detected using hematoxylin-eosin staining.Depression-like behavioral changes were observed in the rat models.E nzyme-linked immunosorbent assay was used to determine the serum level of related targets.RESULTS AND CONCLUSION:Three possible common protein targets were identified based on proteomic and network pharmacology analyses:glutathione transferase(GSTM1),3-phosphoinositide dependent protein kinase 1(PDK1),heat shock protein 90AB1(HSP90AB1).Gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses found that these targets were directly involved in the negative regulation of neuro nal apoptosis,PI3K-Akt signaling pathway,and prostate cancer molecular signaling pathway.Hematoxylin-eosin staining and behavioral tests showed that Jiawei Xiaoyao San improved liver damage and depression-like behaviors in rats.Results from the enzyme-linked immunosorbent assay revealed that GSTM1,PDK1,and HSP90AB1 had co rrective e

关 键 词：网络药理学 蛋白质组学 加味逍遥散 肝癌并发抑郁症 蛋白靶点 

分 类 号：R452[医药卫生—治疗学] R318[医药卫生—临床医学]