广藿香酮对溃疡性结肠炎的抗炎作用及其作用机制研究  

Study on Anti-Inflammatory Effect of Pogostone on Ulcerative Colitis and Its Mechanism

作　　者：李美慧 黄友 付豪 吴孟霞 张月 傅舒[1] 张文静 张臻[1] 傅超美[1] LI Meihui;HUANG You;FU Hao;WU Mengxia;ZHANG Yue;FU Shu;ZHENG Wenjing;ZHANG Zhen;FU Chaomei(School of Pharmacy,Chengdu University of Traditional Chinese Medicine,Chengdu 611137,China)

机构地区：[1]成都中医药大学药学院,四川成都611137

出　　处：《成都大学学报(自然科学版)》2025年第1期1-8,共8页Journal of Chengdu University(Natural Science Edition)

基　　金：国家自然科学基金联合基金重点项目(U21A20409);四川省科技厅科技计划项目(2021YJ0251);四川省中医药管理局中医药科研专项(2021MS109);成都中医药大学杏林学者青年学者专项(QNXZ2019031)。

摘　　要：研究广藿香酮对溃疡性结肠炎(UC)的作用机制.使用葡聚糖硫酸钠建立UC小鼠模型,共有30只雄性ICR小鼠随机分为对照组、模型组、广藿香酮高剂量组(80 mg/kg)、广藿香酮中剂量组(40 mg/kg)和广藿香酮低剂量组(20 mg/kg);药物连续干预7 d后,收集各组小鼠结肠组织;通过苏木精—伊红染色观察结肠组织病理学变化,酶联免疫吸附测定法检测结肠中肿瘤坏死因子-α(TNF-α)和白细胞介素-1β(IL-1β)水平;取结肠组织提取RNA进行转录组测序与分析,获得广藿香酮抗UC的差异基因;通过Swiss TargetPrediction、GeneCards和OMIM数据库获得广藿香酮抗UC的潜在靶点;随后将差异基因和潜在靶点合并得到治疗靶点,进行KEGG富集分析;利用蛋白质—蛋白质互作(PPI)网络筛选核心靶点;运用分子对接、分子动力学模拟及实时荧光定量多聚核苷酸链式反应(RT-PCR)验证核心靶点.结果表明,药效方面,与模型组比较,广藿香酮给药组小鼠UC症状明显改善,结肠组织病理损伤减轻,结肠中炎性细胞因子TNF-α和IL-1β含量显著下调;机制方面,得到180个广藿香酮干预UC的潜在治疗靶点,主要涉及趋化因子、Toll样受体(TLR)、肿瘤坏死因子(TNF)和白细胞介素-17(IL-17)等信号通路,PPI网络筛选出16个核心靶点;分子对接和动力学模拟显示,广藿香酮与核心靶点结合均良好;RT-PCR结果表明,广藿香酮能逆转丝氨酸/苏氨酸蛋白激酶1(AKT1)、表皮因子生长受体(EGFR)和原癌基因蛋白(FOS)等核心靶点在UC小鼠结肠组织中的高表达,基本符合转录组学和网络药理学的预测结果.广藿香酮对小鼠实验性UC具有明显的治疗效果,其潜在作用机制主要为作用AKT1、EGFR和FOS等核心靶点,调控趋化因子、TLR、TNF和IL-17等炎症信号通路.To study the mechanism of pogostone in treating ulcerative colitis(UC),dextran sodium sulfate(DSS) was used to establish a mouse model of UC.30 male ICR mice were randomly divided into control group,model group,and pogostone high-dose group(80 mg/kg),medium-dose group(40 mg/kg) and low-dose group(20 mg/kg).After 7 days of drug intervention,the colon tissue of the mice was collected.Hematoxylin-eosin staining revealed the colon's histopathological alterations,while enzyme-linked immunosorbent assay identified the concentrations of tumor necrosis factor-α(TNF-α) and interleukin-1β(IL-1β) in the mice colon.RNA was extracted from mice colon tissues for transcriptome sequencing to obtain the differential gene of pogostone on UC.The targets of pogostone for UC were obtained by Swiss TargetPrediction,GeneCards and OMIM databases.The differential genes and targets were subsequently combined to obtain therapeutic targets for kyoto encyclopedia of genes and genomes(KEGG) enrichment analysis.The protein-protein interaction(PPI) network was utilized to obtain the core targets.Molecular docking,molecular dynamics simulation,and Real-time PCR(RT-PCR) were used to validate the core targets.The results in terms of drug efficacy showed that compared with the model group,the UC symptoms of mice in each administration group of pogostone were significantly improved,the histopathological damage of the colon was reduced,and the content of inflammatory cytokines TNF-α and IL-1β in the colon was significantly down-regulated.The results of mechanism showed that 180 potential therapeutic targets of pogostone for treating UC were obtained,mainly involving Chemokine,Toll-like receptor(TLR),TNF,IL-17,and other signaling pathways.PPI network screened 16 core targets,and molecular docking and molecular dynamics simulation showed that pogostone was well bound.The RT-PCR results showed that pogostone could reverse the high expression of AKT1,EGFR,FOS in the colon tissues of mice in the model group,which was basically in line with the predi

关 键 词：广藿香酮 UC 转录组学 网络药理学 分子对接 分子动力学模拟 

分 类 号：R285.5[医药卫生—中药学]