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化浊解毒方药治疗溃疡性结肠炎的靶点及疗效因素分析

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基于网络药理学和临床预测模型的技术,探究化浊解毒方药治疗溃疡性结肠炎(UC)的作用机制及疗效影响因素.基于网络药理学预测得到化浊解毒方药治疗UC的有效化学成分、关键靶点蛋白和通路,并通过GEO数据库对关键靶点蛋白进行基因表达差异分析.回顾性分析2019年7月—2021年12月间于河北省中医院住院应用化浊解毒方药口服及灌肠法联合美沙拉嗪治疗的95例UC湿热毒蕴型患者的临床资料,采用多因素逐步Logistic回归分析疗效影响因素,依照分析结果构建模型并验证.化浊解毒方药干预U C的有效化学成分主要包括:槲皮素、山奈酚、β-谷甾醇、豆甾醇、异鼠李素等,具有表达差异的关键靶点蛋白包括RXRA、TNF、NR3C2、XDH、JUN等,治疗过程涉及IL-17信号通路、TNF信号通路、T细胞受体信号通路、Th17细胞分化等通路.多因素逐步Logistics回归分析后,选取发病季节、血沉、红细胞平均体积、红细胞分布宽度、脉象、苔象、中医评分(腹泻)7项指标进行列线图的绘制.标准曲线与校准预测曲线有较好的一致性,AUC(95%CI)为 0.850(0.752~0.948),特异度 0.845,灵敏度 0.792,准确度 0.832,DCA曲线表明该模型具有良好的收益率.结论可知,化浊解毒方药可能是通过调节IL-17、TNF、T细胞受体信号、Th17细胞分化等通路及RXRA、TNF、NR3C2、XDH、JUN等关键靶点蛋白对UC进行干预治疗.基于临床资料构建的临床预测模型具有相对准确性和辨识性,临床应用可获得较好的正向收益.
Analysis of target and curative effect factors of Huazhuo Jiedu prescription in the treatment of ulcerative colitis
Based on the technology of network pharmacology and clinical prediction model,this paper discusses the mechanism and influencing factors of curative effect of Huazhuo Jiedu prescription in the treatment of ulcerative co-litis(UC).Based on the network pharmacological prediction,the effective chemical components,key target pro-teins and pathways of Huazhuo Jiedu traditional Chinese medicine in the treatment of UC were obtained,and the gene expression differences of key target proteins were analyzed through GEO database.The clinical data of 95 pa-tients with UC dampness heat toxin accumulation type who were hospitalized in Hebei Traditional Chinese medicine hospital from July 2019 to December 2021 were analyzed retrospectively.Multivariate stepwise logistic regression was used to analyze the influencing factors of curative effect.Nomogram model was constructed according to the re-sults.The enhanced bootstrap method and ROC curve method are used to verify the predictive value of the model,and the clinical benefit of the model was evaluated by clinical decision curve(DCA).The effective chemical com-ponents of Huazhuo Jiedu prescription in UC mainly include quercetin,kaempferol,β-sitosterol,stigmasterol and isorhamnetin,etc.,the key target proteins include RXRA,TNF,NR3C2,XDH and JUN,etc.,the treatment process involves IL-17 signal pathway,TNF signal pathway,T cell receptor signal pathway,Th 17 cell differentiation and other pathways.After multivariate stepwise logistic regression analysis,seven indexes were selected to draw the no-mogram:season,ESR,MCV,RDW,pulse,moss and TCM score(diarrhea).The standard curve is in good a-greement with the calibration prediction curve.The AUC(95%CI)is 0.850(0.752~0.948),the specificity is 0.845,the sensitivity is 0.792 and the accuracy is 0.832.The DCA curve shows that the model has a good yield.Huazhuo Jiedu prescription may intervene in the treatment of UC by regulating the pathways such as IL-17,TNF,T cell receptor signal,Th17 cell differentiation and key target proteins such as RXRA,TNF,NR3C2,XDH and JUN.The clinical prediction model based on clinical data has relative accuracy and identification,and good positive benefits can be obtained in clinical application.

clinical prediction modelnetwork pharmacologyGEOulcerative colitisHuazhuo Jiedu prescription

程楠、杨玥玮、董佳琪、刘丽然、柳亚杰、杨倩、李博林

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河北中医药大学研究生院,河北石家庄 050200

张家口市第一医院中医科,河北张家口 075000

河北省中医院脾胃病科、河北省浊毒证重点实验室,河北石家庄 050011

临床预测模型 网络药理学 GEO 溃疡结肠炎 化浊解毒方药

国家中医临床研究基地建设项目河北省政府资助临床医学优秀人才培养项目河北省博士后科研资助课题河北省中医药管理局科研计划项目河北省"三三三人才工程"资助项目

国中医药办科技函[2018]131号ZF2023160B20220030422020079C20221097

2024

云南民族大学学报(自然科学版)
云南民族大学

云南民族大学学报(自然科学版)

CSTPCD
影响因子:0.381
ISSN:1672-8513
年,卷(期):2024.33(4)