首页|基于中性粒细胞胞外诱捕网途径探讨胃黏膜肠上皮化生的发生机制及中药预测研究

基于中性粒细胞胞外诱捕网途径探讨胃黏膜肠上皮化生的发生机制及中药预测研究

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目的 探讨中性粒细胞胞外诱捕网(NETs)对胃黏膜肠上皮化生(Intestinal metaplasia,IM)的作用机制及治疗靶点,为中医药防治IM提供新思路和新方向。方法 从公共数据库下载IM及NETs相关数据集,通过免疫浸润分析、差异分析及基因相关性分析获得IM与NETs共表达的关键基因集;采用功能富集分析、蛋白互作网络、分子对接技术及实验验证等方法进一步阐述IM及NETs的相关性;最后将获得的关键基因与Coremine Medical平台相互映射,预测中医治疗IM的有效中药和治法。结果 共筛选出6个IM与NETs形成相关的共表达的差异基因,分别为THBD、HDAC9、FGA、AQP9、DECR1和PIK3CD,这些基因与NETs的3个标记性蛋白(NE、PADI4、MPO)存在不同程度的相关性,其功能主要富集在呼吸爆发与防御反应、纤维蛋白溶解等生物学过程上;中药预测共映射出中医治疗IM的中药112味,按照功效可归为34类,其中清热解毒类中药出现频次最高,其次为活血化瘀药、温里药、补气药等。结论 在IM的病理发生及发展过程中存在NETs,靶标基因NE和THBD可能存在相互关联作用,共同通过NETs通路参与IM进展;健脾化瘀解毒法是中医治疗IM的核心治法,其可能通过抑制NETs的形成,从而减缓IM的发展进程。
Mechanism of Intestinal Metaplasia of Gastric Mucosa and Prediction of Traditional Chinese Medicine Based on Neutrophil Extracellular Traps
Objective To explore the mechanism and therapeutic target of neutrophil extracellular traps(NETs)on intestinal metaplasia(IM)of gastric mucosa,so as to provide new ideas and directions for the prevention and treatment of IM with traditional Chinese medicine.Methods The related datasets of IM and NETs were downloaded from the public database,and the key genes co-expressed by IM and NETs were obtained by immune infiltration analysis,difference analysis and gene correlation analysis,and the correlation between IM and NETs was further expounded by functional enrichment analysis,protein interaction network,molecular docking technique and experimental verification.Finally,the obtained key genes were mapped with Coremine Medical platform to predict the effective traditional Chinese medicine and therapeutic method of IM.Results Six differentially expressed genes related to the formation of IM and NETs were screened,namely THBD,HDAC9,FGA,AQP9,DECR1 and PIK3CD.These genes were correlated with the three marker proteins of NETs(NE,PADI4,MPO),and their functions were mainly concentrated in biological processes such as respiratory burst and defense response,fibrinolysis and so on.The prediction of traditional Chinese medicine shows that there are 112 kinds of traditional Chinese medicine in the treatment of IM,which can be classified into 34 categories according to their efficacy,among which the frequency of traditional Chinese medicine of clearing away heat and detoxification is the highest,followed by drugs for promoting blood circulation and removing blood stasis,medicine for warming inside,medicine for tonifying qi and so on.Conclusion There is NETs in the pathological occurrence and development of IM,and the target genes NE and THBD may be related to each other and participate in the progression of IM through NETs pathway,and the therapeutic method of Jianpi Huayu Jiedu is the core treatment of IM,which may slow down the development of IM by inhibiting the formation of NETs.

Intestinal metaplasiaNeutrophil extracellular trapsDifferentially expressed genesBioinformaticsPrediction of traditional Chinese medicineJianpi Huayu Jiedu Formula

张伟健、吴钰淇、李海文、宋书雅、周荻书、洪欣欣、许艺飞、郭绍举、潘华峰

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广州中医药大学科技创新中心 广州 510006

广州中医药大学第四临床医学院 深圳 518033

深圳市中医院 深圳 518033

肠上皮化生 中性粒细胞胞外诱捕网 差异表达基因 生物信息学 中药预测 健脾化瘀解毒法

国家自然科学基金青年科学基金广东省重点领域研发项目深圳市科创委深圳市科技计划面上项目

821047472020B1111100011JCYJ20230807094659030

2024

世界科学技术-中医药现代化
中科院科技政策与管理科学研究所,中国高技术产业发展促进会

世界科学技术-中医药现代化

CSTPCD北大核心
影响因子:1.175
ISSN:1674-3849
年,卷(期):2024.26(2)
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