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[溃疡性结肠炎活动期关键基因及治疗性中药的生物信息学分析与系统评价]

[Bioinformatics analysis and systematic review of key genes and therapeutic traditional Chinese medicine of ulcerative colitis active stage].

作者信息

Wu Na, Mao Xiang-Kun, Wan Zhi-Ping, Yu Nan, Li Hua-Shan

机构信息

Guang'anmen Hospital, China Academy of Chinese Medical Sciences Beijing 100053, China.

Nanchang Hongdu Hospital of Traditional Chinese Medicine Nanchang 330006, China.

出版信息

Zhongguo Zhong Yao Za Zhi. 2020 Jun;45(11):2677-2686. doi: 10.19540/j.cnki.cjcmm.20200115.501.

Abstract

Data GSE75214 and GSE48959 that contained ulcerative colitis(UC) in the active stage was download from GEO database. Differential genes of UC in the active phase were obtained by using adjusted P<0.05 and |log_2 FC|≥1.5, which was the screening criteria. PPI analysis was performed in the STRING database, and GO and KEGG pathway analysis was performed in DAVID database. Cytoscape was used to visualize differential genes, and calculate key genes in the active phase. Coremine Medical was used to analyze and systematically evaluate traditional Chinese medicines for treating key genes. Finally, 139 differentially expressed genes in the active phase were screened out, which included the 109 up-regulated genes and 30 down-regulated genes. DAVID analyzed that the biology and pathways of these differential genes were mainly concentrated in inflammatory response, immune response, chemokine activity, TNF pathway, NF-κB pathway, and Toll-like receptor pathway. Cytoscape software calculated that IL-6, CXCL8, IL-1β, MMP9, CXCL1, ICAM1, CXCL10, TIMP1, PTGS2 and CXCL9 were the key genes of UC in the active phase. According to Coremine Medical analysis, traditional Chinese medicines for UC in the active stage included Curcumae Longae Rhizoma, Scutellariae Radix, Curcumae Radix had clearing heat clearing damp, reducing fire and detoxifying effects, which was in line with the pathogenesis of UC active stage, and was often used in clinical treatment of dampness-heat diarrhea. Therefore, Huangqin Decoction, which Scutellariae Radix was the principal drug, was selected for systematic evaluation. The evaluation showed that Scutellariae Radix was superior to Western medicine in terms of improving clinical efficiency, reducing inflammatory factors and immunoglobulin levels, with statistically significant differences and fewer adverse reactions. This study provided a new idea for further research on the pathogenesis of UC in the active phase by analyzing the genes and their mechanism of action, and the systematic evaluation of Chinese medicine for the treatment of UC active stage provided a basis for the clinical prevention and treatment of UC by Chinese medicine.

摘要

从基因表达综合数据库(GEO数据库)下载了包含活动期溃疡性结肠炎(UC)的数据集GSE75214和GSE48959。以调整后的P<0.05和|log_2 FC|≥1.5作为筛选标准,获得活动期UC的差异基因。在STRING数据库中进行蛋白质-蛋白质相互作用(PPI)分析,在DAVID数据库中进行基因本体论(GO)和京都基因与基因组百科全书(KEGG)通路分析。使用Cytoscape软件对差异基因进行可视化,并计算活动期的关键基因。利用Coremine Medical分析软件对治疗关键基因的中药进行分析和系统评价。最终筛选出活动期139个差异表达基因,其中上调基因109个,下调基因30个。DAVID分析表明,这些差异基因的生物学功能和通路主要集中在炎症反应、免疫反应、趋化因子活性、肿瘤坏死因子(TNF)通路、核因子κB(NF-κB)通路和Toll样受体通路。Cytoscape软件计算得出,白细胞介素-6(IL-6)、趋化因子配体8(CXCL8)、白细胞介素-1β(IL-1β)、基质金属蛋白酶9(MMP9)、趋化因子配体1(CXCL1)、细胞间黏附分子1(ICAM1)、趋化因子配体10(CXCL10)、金属蛋白酶组织抑制因子1(TIMP1)、前列腺素内过氧化物合酶2(PTGS2)和趋化因子配体9(CXCL9)是活动期UC的关键基因。根据Coremine Medical分析软件,活动期UC的常用中药包括郁金、黄芩、莪术,具有清热燥湿、泻火解毒的功效,符合UC活动期的发病机制,常用于临床湿热泄泻的治疗。因此,选择以黄芩为君药的黄芩汤进行系统评价。评价结果显示,黄芩在提高临床疗效、降低炎症因子和免疫球蛋白水平方面优于西药,差异有统计学意义,且不良反应较少。本研究通过分析UC活动期的基因及其作用机制,为进一步研究UC发病机制提供了新思路,对治疗UC活动期中药的系统评价为中医药临床防治UC提供了依据。

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