首页|中药复方SQQT对胃黏膜解痉多肽表达化生细胞干预作用及其系统生物学机制解析

中药复方SQQT对胃黏膜解痉多肽表达化生细胞干预作用及其系统生物学机制解析

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目的:研究中药复方SQQT对胃黏膜解痉多肽表达化生(SPEM)细胞病理表型的影响,探讨其干预SPEM细胞病理演变的可能效应机制。方法:回顾性分析以SQQT为主方的中药辨证方对临床不同部位胃黏膜癌前病变的干预效果和SPEM细胞分布情况;评估SQQT对小鼠模型SPEM细胞病理表型的影响;利用超高效液相色谱、单细胞RNA转录数据挖掘和网络药理学分析等系统生物学方法构建"成分-靶点"网络图谱,并进行拓扑分析。结果:①中药辨证方可有效减轻胃癌前病变患者胃体黏膜萎缩、肠化、异型增生的程度,抑制胃体黏膜基底部SPEM细胞的形成;②SQQT可显著降低他莫昔芬复合法诱导的增殖型SPEM小鼠胃体黏膜SPEM细胞数量,并有效抑制SPEM细胞Ki67和CD44v9标记蛋白的异常表达;③本研究从复方中共鉴定出27种成分和118个靶点与增殖型SPEM细胞的病理转变密切关联。拓扑分析显示,SQQT主要通过调控细胞能量代谢、核糖体功能、细胞通讯、凋亡信号通路等,影响SPEM细胞的增殖和分化功能。有6种化学成分(柠檬酸、根皮酚、去甲基吴茱萸酰胺、吴茱萸黄碱、橙皮苷和人参皂苷Re)同时参与调节SPEM细胞的线粒体ATP合成电子转运、氧化还原膜转运体活性以及核糖体功能,可能是SQQT调控SPEM细胞病理演变的潜在物质基础。结论:中药复方SQQT通过多种成分对应多个靶点的整体调控作用,实现抑制胃黏膜SPEM细胞异常增殖和分化。
The therapeutic intervention of Chinese herbal formula SQQT on gastric mucosal spasmolytic polypeptide-expressing metaplasia cells and its systematic biological mechanism analysis
Objective:This study aimed to investigate the therapeutic impact of SQQT on the pathological phe-notype of spasmolytic polypeptide-expressing metaplasia(SPEM)cells in the gastric mucosa,and to explore the potential mechanisms underlying its intervention in the pathological evolution of SPEM cells.Methods:Retrospec-tive analysis was conducted to assess SQQT's effect on gastric precancerous lesions and SPEM cell distribution.In a murine model,the effect of SQQT on SPEM cytopathic phenotype was evaluated.A"component-target"net-work map was constructed using chromatography,single-cell RNA data,and network pharmacology analysis,fol-lowed by topological analysis.Results:①SQQT effectively alleviated gastric mucosal atrophy,intestinal metapla-sia,and dysplasia in patients with precancerous gastric lesions,and reduced SPEM cell formation at the gastric mucosal base;②Notably,SQQT significantly reduced the count of SPEM cells in the gastric mucosa of mice in-duced by the tamoxifen compound method,effectively targeting and suppressing the abnormal expression of key marker proteins such as Ki67 and CD44v9.③ This study identified a total of 27 components and 118 targets from the compound that are intimately associated with the pathological transition of proliferating SPEM cells.Topologi-cal analysis revealed that SQQT primarily regulates cellular processes including energy metabolism,ribosomal function,cell communication,and apoptotic signaling pathways,thereby exerting a profound impact on SPEM cell proliferation and differentiation.Intriguingly,six specific chemical constituents—Citric acid,Root bark phenol,Demethylated ruthenic amide,Wu Zhu Yu Huang alkaloid,Hesperidin,and Ginsenoside Re—were implicated in regulating critical biological functions such as mitochondrial ATP synthesis electron transport,redox membrane transporter activity,and ribosome function in SPEM cells,potentially constituting the material basis for com-pound regulation of SPEM cell pathology.Conclusion:The traditional Chinese medicine compound SQQT effec-tively suppresses abnormal proliferation and differentiation of SPEM cells in the gastric mucosa by harnessing the synergistic effects of multiple components targeting diverse biological pathways.

SQQTgastric mucosa inflammation-cancer transformationspasmolytic polypeptide-expressing metaplasiaefficacy observationsystems biology

刘林、王萍、吉海杰、孙元隆、刘炯、唐旭东

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中国中医科学院西苑医院脾胃病研究所(北京,100091)

山西省中医药研究院中心实验室

上海中医药大学附属曙光医院心内科

中国中医科学院西苑医院病理科

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SQQT 胃黏膜炎-癌转化 解痉多肽表达化生 疗效观察 系统生物学

国家自然科学基金中国博士后科学基金面上项目中国博士后科学基金特别资助项目中国中医科学院科技创新工程项目提升高水平中医医院临床研究和成果转化能力试点建设项目

822745112021M6935412022T150731CI2021A01004XYZX0204-03

2024

中国中西医结合消化杂志
华中科技大学同济医学院,中国中西医结合学会消化系统疾病专业委员会,中华中医药学会脾胃病专业委员会

中国中西医结合消化杂志

CSTPCD
影响因子:1.363
ISSN:1671-038X
年,卷(期):2024.32(5)