摘要
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UC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.
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 colitis(UC).Based on the network pharmacological prediction,the effective chemical components,key target proteins 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 patients 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 results.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 components 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,Th17 cell differentiation and other pathways.After multivariate stepwise logistic regression analysis,seven indexes were selected to draw the nomogram:season,ESR,MCV,RDW,pulse,moss and TCM score(diarrhea).The standard curve is in good agreement 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,N
作者
程楠
杨玥玮
董佳琪
刘丽然
柳亚杰
杨倩
李博林
CHENG Nan;YANG Yue-wei;DONG Jia-qi;LIU Li-ran;LIU Ya-jie;YANG Qian;LI Bo-lin(Graduate school,Hebei University of Chinese Medicine,Shijiazhuang 050200,China;Department of Traditional Chinese Medicine,The First Hospital of Zhangjiakou,Zhangjiakou 075000,China;Department of Spleen and Stomach,Hebei Province Hospital of Chinese Medicine,and Hebei Key Laboratory of Turbidity Toxin Syndrome,Shijiazhuang 050011,China)
出处
《云南民族大学学报（自然科学版）》
CAS
2024年第4期443-454,共12页
Journal of Yunnan Minzu University:Natural Sciences Edition
基金
国家中医临床研究基地建设项目(国中医药办科技函[2018]131号)
河北省政府资助临床医学优秀人才培养项目(ZF2023160)
河北省博士后科研资助课题(B2022003042)
河北省中医药管理局科研计划项目(2020079)
河北省“三三三人才工程”资助项目(C20221097).
关键词
临床预测模型
网络药理学
GEO
溃疡结肠炎
化浊解毒方药
clinical prediction model
network pharmacology
GEO
ulcerative colitis
Huazhuo Jiedu prescription
