基于网络药理学探究舒肝宁口服制剂对胆汁淤积性肝损伤小鼠的保护作用  

Protective effect of Shuganning oral preparation on mice with cholestatic liver injury and its mechanism based on network pharmacology

作　　者：张芷欣 李洁 李小飘 张祥令 熊英 何峰 ZHANG Zhixin;LI Jie;LI Xiaopiao;ZHANG Xiangling;XIONG Ying;HE Feng(School of Nursing,Guizhou Medical University,Guian 561113,Guizhou,China;School of Basic Medical Sciences,Guizhou Medical University,Guian 561113,Guizhou,China;School of Pharmacy,Guizhou Medical University,Guian 561113,Guizhou,China)

机构地区：[1]贵州医科大学护理学院,贵州贵安561113 [2]贵州医科大学药学院,贵州贵安561113 [3]贵州医科大学基础医学院,贵州贵安561113

出　　处：《贵州医科大学学报》2025年第3期390-398,共9页Journal of Guizhou Medical University

基　　金：贵州省科技计划项目(黔科合支撑[2023]158)。

摘　　要：目的探讨舒肝宁口服制剂对胆汁淤积性肝损伤小鼠的保护作用及机制。方法通过筛选舒肝宁中药活性成分靶点及胆汁淤积性肝病靶点,两者取交集;采用String数据库和Cytoscape软件分析交集靶点的蛋白互作(protein-protein interaction,PPI)关系,筛选出关键靶点行基因本体(gene ontology,GO)功能和京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)信号通路富集分析;取雄性昆明种小鼠分成对照组、模型组、舒肝宁高、中、低剂量组及熊去氧胆酸组,每组10只;各组动物按各自剂量每日灌胃给药1次,连续10 d;于给药第8天时,除对照组外的各组小鼠建立1-萘异硫氰酸酯(1-naphthyl isothiocyanate,ANIT)诱导的黄疸淤积型肝损伤模型;给药结束后24 h,检测血清中直接胆红素(DBIL)、总胆红素(TBIL)、总胆汁酸(TBA)含量及血清中碱性磷酸酶(AKP)、谷丙转氨酶(ALT)、谷草转移酶(AST)活力;取肝组织行HE染色;检测肝组织超氧化物歧化酶(SOD)活力、丙二醛(MDA)含量;采用Western blot实验检测肝组织中磷脂酰肌醇3-激酶(PI3K)、蛋白激酶B(AKT)表达水平。结果筛选获得舒肝宁中药活性成分对应靶点224个,胆汁淤积性肝病靶点1295个,两者交集靶点90个;交集靶点PPI网络中,AKT1度值最大;PI3K/AKT信号通路是其中重要的信号通路;动物实验结果显示,与对照组比较,模型组小鼠血清中DBIL、TBIL、TBA含量以及PKA、ALT、AST活性均显著升高(P<0.01),肝组织SOD活性明显降低(P<0.01)、MDA含量明显升高(P<0.01);与模型组比较,舒肝宁高、中、低剂量组及熊去氧胆酸组小鼠血清中DBIL、TBIL和TBA含量及PKA、ALT和AST活性均降低(P<0.05或P<0.01),肝组织SOD活性升高(P<0.05,P<0.01)、MDA含量降低(P<0.05,P<0.01);模型组小鼠肝小叶的汇管周围出现肝细胞肿胀、脂肪样变及局灶性坏死,伴有炎细胞浸润;舒肝宁高、中、低剂量组及熊去氧胆酸组小鼠肝组织病理Objective To explore the protective effect of Shuganning oral preparation on mice with cholestatic liver injury and its mechanism.Methods Intersection targets were extracted from the targets of active ingredients in Shuganning traditional Chinese medicine and the targets of cholestatic liver disease.String database and Cytoscape software were performed on intersection targets to analyze protein-protein interaction(PPI)to obtain hub genes for GO function and KEGG signal pathway enrichment analyses.Male KM mice were randomly divided into control group,model group,high-,medium-and low-dose Shuganning groups and ursodeoxycholic acid group(10 mice/group).The mice in each group were intragastrically administered once a day according to their respective doses for 10 consecutive days.On the 8 th day of administration,except for control group,the mice in each group were used to establish a mouse cholestatic liver injury model induced by 1-naphthyl isothiocyanate(ANIT).At 24 hours after the end of administration,the levels of serum direct bilirubin(DBIL),total bilirubin(TBIL),total bile acid(TBA),the activities of serum alkaline phosphatase(AKP),alanine aminotransferase(ALT)and aspartate aminotransferase(AST)were measured.HE staining was conducted on liver tissues.Superoxide dismutase(SOD)activity and malondialdehyde(MDA)content were determined in liver tissues.Western blot was utilized to detect the expression levels of PI3K and AKT in the liver tissues.Results There were 224 identified targets of the active ingredients of Shuganning traditional Chinese medicine,and 1295 targets were identified for cholestatic liver disease,among which,90 targets were intersection targets.In PPI network of intersection targets,AKT1 had the highest degree value.PI3K/AKT signaling pathway was one of the important signaling pathways.The results of animal experiments showed that when compared to control group,model group had the obvious increases in the contents of mouse serum DBIL,TBIL and TBA,the elevated activities of PKA,ALT and AST(P<0.0

关 键 词：网络药理学 舒肝宁 口服制剂 胆汁淤积性肝损伤 小鼠 

分 类 号：R575.5[医药卫生—消化系统]