二肽激肽酶4抑制剂对帕金森病模型细胞形态和增殖的干预作用及其机制  

Intervention effects of DPP-4 inhibitors on morphology and proliferation of model cells with Parkinson's disease and the mechanism

作　　者：伊木然江·苏布哈提 艾尼瓦尔·吾买尔[1] 木塔力甫·艾买提 Yimuranjiang Subuhati;Wumaier Ainiwaer;Mutalifu Aimaiti(College of Pharmacy,Xinjiang Medical University,Urumqi 830017,China;不详)

机构地区：[1]新疆医科大学药学院药理学教研室,乌鲁木齐830017 [2]新疆医科大学中心实验室

出　　处：《山东医药》2023年第29期1-6,共6页Shandong Medical Journal

基　　金：新疆维吾尔自治区自然科学基金资助项目(2022D01C89)。

摘　　要：目的基于体外实验及网络药理学,初步探讨二肽激肽酶4(DPP-4)抑制剂对鱼藤酮(ROT)诱导神经细胞帕金森病(PD)的干预作用及其相关机制。方法神经细胞株PC-12分为对照组、模型组、模型+西格列汀组、模型+利格列汀组、模型+维格列汀组,除对照组外各组均使用ROT建立PD体外模型,模型+西格列汀组、模型+利格列汀组、模型+维格列汀组在使用ROT建模的同时在培养基中分别加入DPP-4抑制剂西格列汀、利格列汀、维格列汀。倒置显微镜观察各组细胞形态学变化,CCK-8法观察各组细胞增殖能力。从Swiss Target Prediction、SEA等数据库分别获取DPP-4抑制剂西格列汀、利格列汀、维格列汀、沙格列汀及阿格列汀的药物靶点,通过DisGeNet、OMIM及GeneCards等数据库获取PD相关的疾病靶点,利用韦恩图将药物与疾病靶点取交集得到DPP-4抑制剂作用于PD的相关靶点。通过String数据库构建蛋白—蛋白相互作用(PPI)网络,选取基因满足度(Degree)值>平均值的基因作为DPP-4抑制剂对PD产生作用的关键靶点,将DPP-4抑制剂作用于PD的关键靶点基因输入到DAVID数据库进行GO基因功能和KEGG作用通路分析。将DPP-4抑制剂治疗PD的关键靶点以及KEGG信号通路导入到Cytoscape 3.7.2软件构建药物—疾病—靶点—通路网络,筛选与PD相关信号通路关系最为密切的靶点作为DPP-4抑制剂治疗PD的核心靶点,采用CB-Dock 2对接平台进行核心靶点的分子对接验证。结果对照组细胞形态完整,增长状态良好,细胞呈多角形,细胞之间类似突触样连接,且突触较长;模型组细胞密度减少,细胞皱缩,细胞与细胞间的突触样连接断裂,且观察到较多圆形的损伤细胞;模型+西格列汀组、模型+利格列汀组、模型+维格列汀组较模型组细胞形态得到改善,恢复到正常状态下的细长、多角形态。模型组细胞存活率低于对照组、模型+西格列汀组、模型+利格列Objective To investigate the protective effects of DPP-4 inhibitors against rotenone-induced neuronal Parkinson's disease and its associated mechanism based on in vitro experiments and network pharmacology.Methods The neural cell line PC-12 was divided into the control group,model group,model+sitagliptin group,model+linagliptin group,and model+vildagliptin group,respectively.After 16-18 h,the PD in vitro models were established using ROT in all groups except the control group.In the model+sitagliptin,model+linagliptin,and model+vildagliptin groups,ROT was added along with sitagliptin,linagliptin,and vildagliptin for intervention.The morphological changes of the cells in each group were observed using the inverted microscope,and the proliferative ability of the cells in each group was ob⁃served by CCK-8.The drug targets of DPP-4 inhibitors,sitagliptin,linagliptin,vildagliptin,saxagliptin and alogliptin,were obtained from Swiss Target Prediction,SEA,Super-Pred,and PharmMapper databases,respectively.PD-related dis⁃ease targets were obtained from DisGeNet,OMIM,and GeneCards databases.A visualization of the common targets of DPP-4 inhibitors acting on PD was obtained from the Venn diagram database.The protein-protein interaction(PPI)net⁃work was constructed through the String database,and the genes with degree values>the average were selected as the key targets of DPP-4 inhibitors on PD,and the key target genes were input into the DAVID database for the analysis of Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway.The key targets of DPP-4 inhibitors for PD treatment and KEGG signaling pathway were imported into Cytoscape 3.7.2 software to construct a drug-disease-targetpathway network,and the targets most closely related to PD-related signaling pathways were screened as the core targets of DPP-4 inhibitors for PD treatment.The CB-Dock 2 docking platform was used to validate the molecular docking of the core target.Results The cells in the control group were morphologically intact,with goo

关 键 词：二肽激肽酶4抑制剂 网络药理学 神经细胞 帕金森病 

分 类 号：R965.1[医药卫生—药理学]