摘要
目的:基于网络药理学和斑马鱼炎症模型探讨凉膈散及其清上、泄下拆方的抗炎作用及配伍机制。方法:通过三种斑马鱼炎症模型、生存曲线分析和组织病理切片实验,验证凉膈散及其清上、泄下拆方的抗炎作用。运用TCMSP数据库筛选出凉膈散及其清上、泄下拆方的有效化学成分及对应靶点,通过GeneCards、DisGeNET等数据库检索炎症相关靶点,将凉膈散及其清上、泄下拆方的有效化学成分靶点与炎症靶点取交集,运用STRING数据库对交集靶点构建蛋白质-蛋白质相互作用(PPI)网络,采用David数据库对潜在靶点进行基因本体论(GO)富集分析和京都基因与基因组百科全书(KEGG)通路富集分析。采用实时荧光定量PCR法检测关键靶点的基因表达情况。结果:斑马鱼炎症模型实验结果表明,与正常对照组比较,模型对照组斑马鱼中性粒细胞显著向损伤部位迁移聚集,卵黄囊显微注射LPS后存活时间缩短,死亡率显著升高(P<0.01);与模型对照组比较,地塞米松、不同浓度凉膈散、清上和泄下方均能显著抑制炎症反应,减少中性粒细胞的迁移,延长卵黄囊显微注射LPS后斑马鱼的存活时间,提高其生存率(P<0.05或P<0.01);与凉膈散全方相比,清上、泄下方抑制中性粒细胞迁移的作用减弱(P<0.05或P<0.01),且两拆方表现出协同作用(CI<1),清上、泄下方对LPS注射斑马鱼卵黄囊后的生存保护作用减弱(P<0.01),凉膈散全方作用最佳。网络药理学分析结果显示,凉膈散全方有176个有效化学成分,如连翘苷、槲皮素、山柰酚、木犀草素等,对应266个靶点;清上方有74个有效化学成分,如栀子苷、槲皮素、汉黄芩素、刺槐素等,对应233个靶点;泄下方有109个有效化学成分,如大黄素、大黄酸、谷甾醇等,对应234个靶点。炎症性疾病相关靶点有10933个。两者交集靶点共168个。通过PPI网络图筛选出核心靶点有蛋白激酶B(AKT1)、肿瘤�
Objective::To investigate the anti-inflammatory effects and compatibility mechanisms of Liangge San(凉膈散)and its Qingshang(清上)or Xiexia(泄下)decomposed prescription based on network pharmacology and zebrafish inflammation model.Methods:Three zebrafish inflammation models,survival analysis,and histopathological section experiment were used to verify the anti-inflammatory effects of Liangge San and its Qingshang or Xiexia decomposed prescription.The TCMSP database was used to screen out the effective chemical constituents and corresponding targets of Liangge San and its Qingshang or Xiexia decomposed prescription.Inflammation-related targets were searched in databases such as GeneCards and DisGeNET,and the intersection of the effective chemical constituent targets of Liangge San and its Qingshang or Xiexia decomposed prescription and inflammation targets was selected.The STRING database was used to construct a protein-protein interaction(PPI)network for the intersecting targets.Gene ontology(GO)enrichment analysis and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis were performed on potential targets using the David database.Real-time fluorescence quantification polymerase chain reaction(PCR)was used to detect the gene expression levels of key targets.Results:The experimental results of the zebrafish inflammation model showed that compared with the normal control group,neutrophils of the zebrafish migrated to the injured site significantly,the survival time was shortened after microinjection of LPS into the yolk sac,and the mortality rate was significantly increased in the model group(P<0.01).Compared with the model group,dexamethasone and different concentrations of Liangge San and its Qingshang or Xiexia decomposed prescription could significantly inhibit the inflammatory response,reduce the migration of neutrophils,prolong the survival time of zebrafish after microinjection of LPS into yolk sac,and improve the survival rate(P<0.05 or P<0.01).Compared with the Liangge San presc
作者
姜丽
邹丽芳
郑晓婵
郭新邓
梁芷晴
余林中
刘俊珊
JIANG Li;ZOU Lifang;ZHENG Xiaochan;GUO Xindeng;LIANG Zhiqing;YU Linzhong;LIU Junshan(Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics,School of Traditional Chinese Medicine,Southern Medical University,Guangzhou 510515)
出处
《中药药理与临床》
CAS
CSCD
北大核心
2024年第9期2-10,共9页
Pharmacology and Clinics of Chinese Materia Medica
基金
国家自然科学基金资助项目(编号:82274398)
广东省高等学校珠江学者岗位计划资助项目(编号:GDHVPS2018)
中华中医药学会“青年托举”人才项目(编号:2019-QNRC2-C14)。
关键词
凉膈散
炎症
治法
网络药理学
斑马鱼
Liangge San(凉膈散)
Inflammation
Therapeutic method
Network pharmacology
Zebrafish
