基于网络药理学及动物实验探究白香丹胶囊对大鼠焦虑样行为的作用及其机制  

Effect of Baixiangdan capsule on anxiety-like behavior in rats and its mechanism explored via network pharmacology and animal experiments

作　　者：曲嵩霖 穆晓飞 刘艳芬 李梦霞 郭英慧 QU Songlin;MU Xiaofei;LIU Yanfen;LI Mengxia;GUO Yinghui(College of Traditional Chinese Medicine,Shandong University of Traditional Chinese Medicine,Jinan 250355,China;Institute of Basic Theory of Traditional Chinese Medicine,Chinnese Academy of Traditional Chinese Medicine,Beijing 100700,China;Rizhao Central Hospital,Rizhao 276800,China;Tengzhou Central People's Hospital,Tengzhou 277500,China;Department of Pharmacy,Dongying District High-tech Entrepreneurship Service Center,Dongying 257000,China;Laboratory of Liver Viscera-State&Syndrome of Emotional Disease,Shandong University of Traditional Chinese Medicine,Jinan 250355,China)

机构地区：[1]山东中医药大学中医学院,山东济南250355 [2]中国中医科学院中医基础理论研究所,北京100700 [3]日照市中心医院药学部,山东日照276800 [4]滕州市中心人民医院儿科药房,山东滕州277500 [5]东营区高新技术创业服务中心,山东东营257000 [6]山东中医药大学肝脏象与情志病证实验室,山东济南250355

出　　处：《中国病理生理杂志》2025年第3期492-500,共9页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金面上项目(No.82074293);国家自然科学基金青年项目(No.81202616);山东省研究生教育教学改革研究项目(No.SDYJSJGC2024063);山东省研究生精品和优质专业学位教学案例库项目(No.SDYAL2024147)。

摘　　要：目的:运用网络药理学技术和焦虑大鼠模型探究白香丹胶囊(Baixiangdan capsule,BXD)对焦虑样情绪的干预作用及深层干预机制。方法:利用网络药理学方法筛选BXD干预焦虑模型作用靶点,对靶点进行GO富集和KEGG通路分析;观察BXD对足底电击刺激大鼠焦虑模型行为学,血清c-Jun氨基末端激酶抑制因子(c-Jun N-terminal kinase inhibitor,JIK)含量,海马和下丘脑中c-Jun氨基末端激酶(c-Jun N-terminal kinase,JNK)、磷酸化JNK(phosphorylated JNK,p-JNK)、JIK等蛋白水平变化的影响。结果:(1)筛选出多巴胺D1/D3受体等97个为交集靶点;GO富集分析发现参与儿茶酚胺结合、受体激活、信号传导等分子功能的靶蛋白富集程度较高;KEGG通路分析发现多巴胺能神经突触(15%)、神经活性配体-受体相互作用(18%)等神经受体配体通路占比高。(2)动物实验方面,与模型组比较,使用BXD及地西泮治疗后,旷场实验总路径减少(P<0.01),而中央区进入次数增加(P<0.05),高架十字迷宫实验中开放臂进入次数比和开放臂停留时间比亦增加(P<0.01),p-JNK/JNK比值降低,JIK表达水平则升高(P<0.05)。结论:中药BXD可减轻模型大鼠焦虑样行为,具有多成分、多靶点、多通路的特点,可能通过调控JIK/JNK等信号通路发挥作用。AIM:This study aimed to utilize network pharmacology and an anxiety rat model to investigate the intervention targets and underlying mechanisms of Baixiangdan capsule(BXD)in the treatment of anxiety-like behavior.METHODS:We screened the action targets of BXD on the anxiety model using network pharmacology,followed by Gene Ontology(GO)enrichment and the Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis of the identified targets.Additionally,we evaluated the effects of BXD on rat anxiety behaviors induced by foot shock,with measurement of serum level of c-Jun N-terminal kinase inhibitor(JIK),and the protein levels of c-Jun N-terminal kinase(JNK),phos-phorylated JNK(p-JNK)and JIK in the left hippocampus and hypothalamus.RESULTS:A total of 97 targets,including the dopamine D1/D3 receptors,were identified as intersection targets.GO enrichment analysis indicated that target proteins were significantly involved in molecular functions such as catecholamine binding,receptor activation,and signal transduction.KEGG pathway analysis revealed that neural receptor-ligand pathways,including dopaminergic synapses(15%)and neuroactive ligand-receptor interaction(18%),were notably represented.In behavioral experiments,BXD and diazepam treatments significantly reduced total path in the open-field test(P<0.01),while the number of entries into the central region increased(P<0.05).Additionally,the percentage of entry times of the open arm and the percentage of time spent in the open arm were also increased(P<0.01).Furthermore,BXD treatment led to decreased ratio of p-JNK/JNK and increased level of JIK(P<0.05).CONCLUSION:The traditional Chinese medicine BXD demonstrates a promising efficacy in alleviating anxiety-like behaviors in model rats.It operates through a multi-component,multi-target,and multi-pathway approach,primarily by modulating the JIK/JNK signaling pathway.

关 键 词：白香丹胶囊 焦虑 C-JUN氨基末端激酶 c-Jun氨基末端激酶抑制因子 网络药理学 

分 类 号：R285.5[医药卫生—中药学] R749.7+2[医药卫生—中医学] R363