基于网络药理学探究地锦草防治溃疡性结肠炎的作用机制  

Study on the Mechanism of Euphorbiae humifusae Herba in the Treatment of Ulcerative Colitis Based on Network Pharmacology

作　　者：王辉钦 段莹莹 杨彦平 杨苗 崔晓文[4] 崔一喆[1] WANG Huiqin;DUAN Yingying;YANG Yanping;YANG Miao;CUI Xiaowen;CUI Yizhe(College of Animal Science and Veterinary Medicine,Heilongjiang Bayi Agricultural University,Daqing 163316,China;Mudanjiang Animal Husbandry and Veterinary Technical Service Center of Heilongjiang Province,Mudanjiang 157000,China;Xi’an Guolian Quality Inspection/Xi’an Yutian Agricultural Technology Incorporated Company,Xi’an 710086,China;Heilongjiang Vocational College for Nationalities,Harbin 150066,China)

机构地区：[1]黑龙江八一农垦大学动物科技学院,大庆163316 [2]黑龙江省牡丹江市畜牧兽医技术服务中心,牡丹江157000 [3]西安·国联质检/西安雨田农业科技股份有限公司,西安710086 [4]黑龙江民族职业学院,哈尔滨150066

出　　处：《中国畜牧兽医》2024年第5期2154-2168,共15页China Animal Husbandry & Veterinary Medicine

基　　金：黑龙江省双一流特色学科平台项目(HLJ2022TSXK)。

摘　　要：【目的】基于网络药理学并结合分子对接方法分析地锦草防治溃疡性结肠炎(UC)的活性成分和靶点,探究其潜在机制,进而保护动物肠道。【方法】利用TCMSP数据库获取地锦草的活性成分及对应药物靶点。通过GeneCards、DisGeNET、TTD、PharmGKB和DrugBank数据库获取疾病靶点。药物靶点和疾病靶点取交集获取潜在靶点,分别借助STRING和DAVID数据库对潜在靶点进行蛋白互作(PPI)分析及GO功能和KEGG通路富集分析。借助AutoDock 1.5.7软件进行分子对接验证,利用PyMOL软件将对接结果可视化。通过体内试验利用30只BALB/c小鼠制作葡聚糖硫酸钠(DSS)诱导的UC模型,设置对照组、模型组、地锦草低(5 mg/mL)、高(15 mg/mL)剂量组、美沙拉嗪组(52 mg/mL)。除对照组外,其余各组小鼠连续7 d自由饮用3%DSS诱导UC模型,各给药组小鼠每天灌胃1次,根据小鼠体重灌胃相应剂量的药物0.1 mL/10 g,对照组和模型组小鼠灌胃等体积无菌生理盐水,连续7 d,测其体重变化、疾病活动指数(DAI)评分和结肠长度,检测肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL6)和IL10含量。【结果】地锦草主要活性成分有山柰酚、4’-5二羟基黄酮和鞣花酸等,对应的药物靶点256个,疾病靶点4265个,潜在靶点128个,核心靶点7个。GO功能富集涉及对活性氧的反应、对氧化应激的反应、炎症反应、膜筏、小窝、激酶调节剂活性等。KEGG信号通路涉及PI3K-Akt和TNF信号通路等。分子对接结果显示,山柰酚和过氧化物酶体增殖物激活受体γ(PPARG)、4’,5-二羟基黄酮和PPARG、鞣花酸和丝氨酸/苏氨酸蛋白激酶1(AKT1)、鞣花酸和IL6具有较强结合潜力。体内试验结果表明,与对照组相比,模型组小鼠体重严重下降,严重的甚至出现水样血便,DAI评分极显著升高(P<0.01),结肠组织的黏膜层及黏膜下层出现大量炎性细胞浸润,甚至有小溃疡的出现,表明小鼠UC造模成功。与模�【Objective】Based on network pharmacology and molecular docking,the active ingredients and targets of Euphorbiae humifusae herba in the prevention and treatment of ulcerative colitis(UC)were analyzed,and its potential mechanism was explored to protect the intestinal tract of animals.【Method】The active ingredients and corresponding drug targets of Euphorbiae humifusae herba were obtained by TCMSP database.Disease targets were obtained from GeneCards,DisGeNET,TTD,PharmGKB and DrugBank databases.Potential targets were obtained by intersecting drug targets and disease targets,and the protein-protein interaction(PPI)analysis and GO function and KEGG pathway enrichment analysis of potential targets were performed by STRING and DAVID databases,respectively.AutoDock 1.5.7 software was used for molecular docking verification,and PyMOL software was used to visualize the docking results.Sodium dextran sulfate(DSS)-induced UC model was established in 30 BALB/c mice in vivo.Control group,model group,Euphorbiae humifusae herba low(5 mg/mL),high dose group(15 mg/mL)and mesalazine group(52 mg/mL)were set up.Except for control group,mice in the other groups were free to drink 3%DSS to induce UC model for 7 d.Mice in the drug treatment group was intragastrically administered with 0.2 mL of the corresponding dose once a day.Mice in control and model groups were intragastrically administered with the same volume of sterile normal saline for 7 d.The changes of body weight,disease activity index(DAI)score and colon length were measured,and the contents of tumor necrosis factor-α(TNF-α),interleukin-6(IL6)and IL10 were detected.【Result】The main active ingredients of Euphorbiae humifusae herba were kaempferol,4’-5-dihydroxyflavone and ellagic acid,with 256 corresponding drug targets,4265 disease targets,128 potential targets and 7 core targets.GO functional enrichment involved response to reactive oxygen species,response to oxidative stress,inflammatory response,membrane raft,cave,kinase regulator activity,etc.KEGG signali

关 键 词：地锦草 溃疡性结肠炎 网络药理学 分子对接 作用机制 

分 类 号：S859.7[农业科学—临床兽医学] R285[农业科学—兽医学]