黄芪苷粉末在治疗Hirschsprung病中的潜在效果和作用机制。
The potential effects and mechanism of echinacoside powder in the treatment of Hirschsprung's Disease.
发表日期:2023 Jun 27
作者:
Enyang He, Yuhang Jiang, Diwei Wei, Yifan Wang, Wenjing Sun, Miao Jia, Bowen Shi, Hualei Cui
来源:
CLINICAL PHARMACOLOGY & THERAPEUTICS
摘要:
手术后并发症,如肠梗阻和肠道炎症,会对先天性巨结肠患者的预后产生不良影响。本研究旨在研究指南参芪甙的潜在靶点及其机制,以改善先天性巨结肠患者的预后。通过分析GSE96854数据集和OMIM、DisGeNET、Genecard和NCBI四个数据库获得与该疾病相关的基因。通过三个数据库(PharmMapper、Drugbank和TargetNet)获得指南参芪甙的靶点。通过分子对接验证疾病基因和药物靶点的交集。利用免疫组织化学进一步探究对接靶点的表达。本研究使用富集分析探究参芪甙对基因的作用机制。最终确定了CA1、CA2、CA9、CA12、DNMT1、RIMS2、RPGRIP1L和ZEB2为核心靶点。除了ZEB2主要在脑组织中表达外,其余七个基因在胃肠道中表达具有组织特异性和高表达性。RIMS2在全癌中具有高突变现象,同时建立了包含八个基因的验证ceRNA网络。这些核心基因参与多种信号通路,包括一碳代谢过程、碳酸酐酶活性等。本研究有助于进一步了解参芪甙的药理机制,并为指导先天性巨结肠的治疗提供新的指导和思路。
Possible complications, such as intestinal obstruction and inflammation of the intestinal tract, can have a detrimental effect on the prognosis after surgery for Hirschsprung disease. The aim of this study was to investigate the potential targets and mechanisms of action of echinacoside to improve the prognosis of Hirschsprung disease. Genes related to the disease were obtained through analysis of the GSE96854 dataset and four databases: OMIM, DisGeNET, Genecard and NCBI. The targets of echinacoside were obtained from three databases: PharmMapper, Drugbank and TargetNet. The intersection of disease genes and drug targets was validated by molecular docking. The valid docked targets were further explored for their expression by using immunohistochemistry. In this study, enrichment analysis was used to explore the mechanistic pathways involved in the genes. Finally, we identified CA1, CA2, CA9, CA12, DNMT1, RIMS2, RPGRIP1L and ZEB2 as the core targets. Except for ZEB2, which is predominantly expressed in brain tissue, the remaining seven genes show tissue specificity and high expression in the gastrointestinal tract. RIMS2 possesses a high mutation phenomenon in pan-cancer, while a validated ceRNA network of eight genes was constructed. The core genes are involved in several signaling pathways, including the one-carbon metabolic process, carbonate dehydratase activity and others. This study may help us to further understand the pharmacological mechanisms of echinacoside and provide new guidance and ideas to guide the treatment of Hirschsprung disease.