| 引用本文:张伟健1，2，李诗婷1，李俊怡3，陈楠1，4，罗柳茹4，洪欣欣4，许艺飞4，潘华峰2，李海文4，郭绍举4.基于细胞衰老探讨胃黏膜肠上皮化生的发生机制及中药预测研究[J].世界中医药,2024,(23):. |
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| 基于细胞衰老探讨胃黏膜肠上皮化生的发生机制及中药预测研究 |
| Mechanism of Gastric Mucosal Intestinal Metaplasia and Chinese Medicine Prediction Based on Cell Senescence |
| 投稿时间：2023-12-31 |
| DOI：10.3969/j.issn.1673-7202.2024.23.017 |
| 中文关键词: 肠上皮化生 胃癌前病变 细胞衰老 慢性炎症反应 炎-癌转化 差异基因 中药预测 健脾化瘀解毒法 |
| English Keywords:Intestinal metaplasia Gastric precancerous lesions Cell senescence Chronic inflammation Inflammatory-cancer transformation Differential gene Chinese medicine prediction Tonifying spleen,resolving stasis,and removing toxin method |
| 基金项目:国家自然科学基金面上项目（82374348）；广东省基础与应用基础研究基金省企联合基金-面上项目（2022A1515220071）；广东省重点领域研发项目（2020B1111100011）；深圳市“医疗卫生三名工程”项目(SZZYSM202211002)；深圳市科技计划项目（JCYJ20230807094659030） |
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| 中文摘要: |
| 目的：探讨细胞衰老（CS）对胃黏膜肠上皮化生（IM）的影响及调控机制，为中医药防治IM提供新思路。方法：从公共数据库中下载并构建CS与IM共表达核心基因集；采用免疫浸润分析、功能富集分析、基因相关性分析及蛋白质-蛋白质相互作用网络等方法分析CS与IM的相关性；通过Coremine Medical平台映射中医治疗IM的有效中药并对其功效及性味归经进行统计。结果：免疫浸润分析显示肠上皮化生组中浆细胞的浸润水平显著高于正常组（P=0.025 4）。功能富集分析提示IM与CS共表达的80个核心差异基因主要富集在NAD生物合成过程、细胞命运和癌症的转录失调等CS相关通路上。提取出IM与CS共表达的10个枢纽基因（CEBPA、LGALS3、ANPEP等），枢纽基因与IM相关标志基因表达均呈现一定程度的相关性（P<0.05）。中药预测分析共映射出用于治疗IM的潜在中药56味，涉及经脉11条，其中紫草出现的频次最高（2次）；按照功效分类可归为33类，其中息风止痉药出现频次最高（6次），其次为补气药、活血化瘀药和清热凉血药等（均为4次）。结论：CS介导的慢性持续性炎症促进IM发生发展，IM与CS共表达的枢纽基因可能通过激活炎症相关CS，从而与IM特异性标记分子发生相互作用，促进IM进展；“健脾化瘀解毒法”是中医治疗IM的有效治法。 |
| English Summary: |
| To investigate the impact of cell senescence(CS) on gastric mucosal intestinal metaplasia(IM) and its regulatory mechanisms，providing new insights for the prevention and treatment of IM using traditional Chinese medicine(TCM).Methods:Core gene sets for the co-expression of CS and IM were downloaded and constructed from public databases.The correlation between CS and IM was analyzed using immune infiltration analysis，functional enrichment analysis，gene correlation analysis，and protein-protein interaction networks.The Coremine Medical platform was used to map effective Chinese medicines for treating IM and to statistically analyze their therapeutic properties，flavor，nature，and meridian tropism.Results:Immune infiltration analysis showed that the level of plasma cell infiltration in the IM group was significantly higher than that in the normal group(P=0.025 4).Functional enrichment analysis indicated that the 80 core differential genes co-expressed between IM and CS were mainly enriched in CS-related pathways，including NAD biosynthesis，cell fate，and transcriptional dysregulation in cancer.Ten hub genes(CEBPA，LGALS3，ANPEP，etc.) co-expressed between IM and CS were identified，and the expression of these hub genes showed a certain degree of correlation with IM-related marker genes(P<0.05).Chinese medicine prediction analysis identified 56 potential Chinese medicines for treating IM，involving 11 meridians，with Arnebiae Radix appearing most frequently(2 times).The Chinese medicines were categorized into 33 efficacy groups，with the highest frequency of usage in “wind-extinguishing and convulsions-stopping” drugs(6 times)，followed by “qi-tonifying”“blood-activating and stasis-removing”，and “heat-clearing and blood-cooling” drugs(all 4 times).Conclusion:Chronic persistent inflammation mediated by CS promotes the occurrence and development of IM.The hub genes co-expressed between IM and CS may interact with IM-specific molecular markers by activating inflammation-related CS，thus facilitating the progression of IM.The “tonifying the spleen，resolving stasis，and removing toxin” method is an effective approach in TCM for treating IM. |
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