基于网络药理学与实验验证探究陈皮苷治疗溃疡性结肠炎的作用机制  

Exploration on the mechanism of hesperidin in the treatment of ulcerative colitis based on network pharmacology and experimental verification

作　　者：陆萌 石学魁 崔晓慧 王妍 LU Meng;SHI Xuekui;CUI Xiaohui;WANG Yan(Department of Pathogenic Biology,Mudanjiang Medical University,Mudanjiang,Heilongjiang 157011,China;Hongqi Hospital Affiliated to Mudanjiang Medical University,Mudanjiang,Heilongjiang 157011,China)

机构地区：[1]牡丹江医科大学病原生物学教研室,黑龙江牡丹江157011 [2]牡丹江医科大学附属红旗医院,黑龙江牡丹江157011

出　　处：《热带医学杂志》2024年第7期932-938,F0004,共8页Journal of Tropical Medicine

基　　金：黑龙江省省属高等学校基本科研业务费(2018⁃KYYWFMY⁃0036);牡丹江医学院博士科研启动基金(2021⁃MYBSKY⁃029)。

摘　　要：目的分别采用网络药理学及动物实验两种方式,初步探究陈皮苷治疗溃疡性结肠炎(UC)的作用机制。方法通过SwissTargetPrediction数据库筛选出陈皮苷的相关作用靶点。使用OMIM、GeneCards数据库查找与溃疡性结肠炎对应的靶点信息。利用STRING在线数据库,将药物靶点与疾病靶点匹配后取交集靶点,构建蛋白相互作用(PPI)网络模型。利用Metascape数据库对交集靶点进行GO富集以及KEGG通路富集分析。将50只SPF级ICR小鼠随机分为对照组、模型组、美莎拉嗪组、陈皮苷低剂量组(200 mg/kg)、陈皮苷高剂量组(400 mg/kg),每组10只。使用葡聚糖硫酸钠(DSS)诱导小鼠成为UC模型并按分组不同给药,于给药第7天处死小鼠并取材。取材后对各组小鼠进行疾病活动指数(DAI)评分,并比较各组小鼠体重变化及结肠长度差异;苏木素-伊红(HE)染色观察各组小鼠结肠组织病理学变化;通过ELISA法检测小鼠血清中白细胞介素6(IL⁃6)、肿瘤坏死因子-α(TNF⁃α)水平;采用气相质谱-色谱联用法检测小鼠肠内容物中短链脂肪酸(SCFAs)的含量。结果网络药理学结果显示,陈皮苷治疗UC的相关靶点有15个,通过PPI网络模型可得出ESR1、ALB、ACE等可能是陈皮苷治疗UC的主要靶点,并通过GO及KEGG富集分析获得陈皮苷治疗UC的核心信号通路。动物实验结果证明,陈皮苷干预后的UC小鼠模型DAI评分降低,体重减轻程度有所缓解,结肠长度增长,差异均有统计学意义(F=4.725、11.990、109.400,P均<0.05)。与模型组相比,陈皮苷干预后的UC小鼠血清IL⁃6、TNF⁃α水平降低(F=167.700、154.800,P均<0.05),肠内容物乙酸、丁酸、丙酸、己酸、戊酸、异丁酸、异戊酸数量均有不同程度的增加,且丁酸、戊酸含量的增加较为显著(F=3.440、8.374,P均<0.05)。结论陈皮苷可通过调节主要靶点、增加小鼠肠内容物SCFAs的数量等来改善UC症状。Objective To explore the mechanism of hesperidin in treating ulcerative colitis(UC)by using network pharmacology and animal experiment.Methods The related targets of hesperidin were screened by SwissTargetPrediction database.The target information corresponding to ulcerative colitis was found by using OMIM and GeneCards databases.Using STRING online database,the drug targets and disease targets were matched,and then the intersection targets were selected to construct a protein⁃protein interaction(PPI)network model.GO enrichment and KEGG pathway enrichment of intersection targets were analyzed by R language.Fifty SPF ICR mice were randomly divided into control group,model group,mesalazine group,low⁃dose group of hesperidin(200 mg/kg),and high⁃dose group of hesperidin(400 mg/kg),10 mice/group.Using DSS to induce mice to become UC model,the mice were killed on the seventh day of modeling and the samples were take,the disease activity index(DAI)of mice in each group was scored,and the weight change and colon length difference of mice in each group were compared.HE staining was used to observe the histopathological changes of colon of mice in each group.The levels of interleukin 6(IL⁃6)and tumor necrosis factor⁃α(TNF⁃α)in serum of mice were detected by ELISA.The content of short⁃chain fatty acids(SCFAs)in intestinal contents of mice was detected by gas mass spectrometry⁃chromatography.Results The results of network pharmacology showed that there were 15 related targets of hesperidin in the treatment of UC.Through PPI network model,it was concluded that ESR1,ALB and ACE might be the main targets of hesperidin in the treatment of UC,and the core signal pathway of hesperidin in the treatment of UC was obtained through GO and KEGG enrichment analysis.The results of animal experiments showed that DAI score of UC mouse model was decreased,weight loss was alleviated,colon length was increased,the differences were statistically significant(F=4.725,11.990,109.400;all P<0.05).Compare with that model group,seru

关 键 词：陈皮苷 溃疡性结肠炎 葡聚糖硫酸钠 网络药理学 短链脂肪酸 

分 类 号：R574.62[医药卫生—消化系统]