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本研究旨在探讨加味七方胃痛颗粒阻断胃癌前病变(precancerous lesions gastric cancer, PLGC)“炎癌转化”的分子机制，明确其对胃癌前病变的调控作用。本研究通过复合造模法构建PLGC大鼠(Rattus norregicus)模型，随机分为对照组、模型组、维酶素组及中药组。采用HE染色法评估胃黏膜病理学改变，采用免疫组织化学技术检测p53、 Ki-67蛋白表达；通过转录组测序筛选差异表达基因(differentially expressed genes, DEGs),对DEGs进行功能注释和KEGG富集分析，并对富集到的关键信号通路进行验证。研究结果显示，与空白组大鼠相比，模型组大鼠体质量和3 h进食量均显著降低(P<0.01),胃黏膜腺体萎缩明显，Ki-67、 p53蛋白表达水平升高(P<0.01);与模型组相比，中药组和维酶素组的体质量和3 h进食量显著增加(P<0.01),胃黏膜腺体萎缩改善，炎性细胞浸润数量减少，Ki-67、 p53蛋白表达水平降低(P<0.01)。转录组学测序显示，和模型组相比，空白组中发现了1 197个DEGs;和模型组相比，中药组中有1 298个DEGs。对两组DEGs进行多基因富集可视化，发现PI3K-Akt信号通路显著富集。Western blot结果显示，与正常组大鼠胃组织相比，模型组大鼠胃组织p-PI3K、 p-Akt相对表达水平显著升高(P<0.05);与模型组相比，维酶素组及中药组大鼠胃组织的p-PI3K、 p-Akt相对表达水平显著降低(P<0.05)。本研究发现加味七方胃痛颗粒能有效改善PLGC模型大鼠一般情况及胃黏膜病理状态，降低大鼠血清中的炎症因子IL-6和TNF-α的水平，以及胃组织中“炎癌转化”相关蛋白p53和Ki-67的表达水平，阻断大鼠胃“炎癌转化”的进程，其具体机制可能与调控PI3K-Akt信号通路有关。
Abstract：This study aims to investigate the molecular mechanism of Modified Qifang Weitong Granules in preventing the "inflammation-cancer transformation" of precancerous lesions gastric cancer(PLGC), and to clarify its regulatory effect on precancerous lesions gastric cancer. A PLGC rat(Rattus norregicus) model were constructed using composite modeling method and the rats were randomly divided into control group, model group, Vitacoenzyme group, and Chinese medicine group. HE staining was used to evaluate the pathological changes of gastric mucosa, and immunohistochemistry technique was performed to detect the expression of p53 and Ki-67 proteins. Differentially expressed genes(DEGs) were screened through transcriptome sequencing, and functional annotation and KEGG enrichment analysis were conducted for the DEGs. The enriched key signaling pathways were also verified. The results showed that compared with the blank group, the rats in the model group had significantly reduced body weight and 3-hour food intake(P<0.01), obvious atrophy of gastric mucosal glands, and increased expression of Ki-67 and p53 proteins(P<0.01). Compared with the model group, the Chinese medicine group and the Vitacoenzyme group had significantly increased body weight and 3-hour food intake(P<0.01), improved atrophy of gastric mucosal glands, and reduced inflammatory cell infiltration, and the expression of Ki-67 and p53 proteins was decreased(P<0.01). Transcriptome sequencing revealed 1 197 DEGs between the blank group and the model group, and 1 298 DEGs between the Chinese medicine group and the model group. Visualization of multigene enrichment for both groups of DEGs revealed significant enrichment of PI3K-Akt signaling pathway.Western blot results showed that compared with the gastric tissue of normal rats, the relative expression levels of p-PI3K and p-Akt in the gastric tissue of the model group were significantly increased(P<0.05). Compared with the model group, the relative expression levels of p-PI3K and p-Akt in the gastric tissues of rats in the Vitacoenzyme group and the Chinese medicine group were significantly reduced(P<0.05). In conclusion, the present study reveals that Modified Qifang Weitong Granules can effectively improve the general condition and pathological state of gastric mucosa in PLGC model rats, reduce the levels of inflammatory factors IL-6 and TNF-α in serum and the expression of "inflammation-cancer transformation" related proteins p53 and Ki-67 in gastric tissues, and block the process of "inflammation-cancer transformation". The mechanism may be rela-ted to the regulation of PI3K-Akt signaling pathway.
陈美琳，2019.七方胃痛方治疗肝胃不和型慢性萎缩性胃炎的临床疗效观察，硕士学位论文.南宁：广西中医药大学.(CHEN M L,2019.Clinical observation on the treatment of chronic atrophic gastritis with disharmony between liver and stomach with Qifang Weitong recipe,Thesis for M.S.Nanning:Guangxi University of Chinese Medicine.)
陈硕，李江辉，洪嘉辉，等，2024.消痞汤对脾胃虚弱证慢性萎缩性胃炎患者的临床疗效.中成药，46(10):3288-3292.[CHEN S,LI J H,HONG J H,et al.,2024.Clinical effects of Xiaopi Decoction on patients with chronic atrophic gastritis of Spleen-Stomach Weakness Pattern.Chinese Traditional Patent Medicine,46(10):3288-3292.]
房静远，杜奕奇，刘文忠，等，2023.中国慢性胃炎诊治指南(2022年，上海).胃肠病学，28(3):149-180.[FANG J Y,DU Y Q,LIU W Z,et al.,2023.Guidelines for diagnosis and treatment of chronic gastritis in China(2022,Shanghai).Chinese Journal of Gastroenterology,28(3):149-180.]
国家消化系疾病临床医学研究中心，国家消化道早癌防治中心联盟，中华医学会消化病学分会幽门螺杆菌学组，等，2020.中国胃黏膜癌前状态和癌前病变的处理策略专家共识(2020年).中华消化杂志，40(11):731-741.[National Clinical Medical Research Center for Digestive Diseases (Shanghai),National Alliance of Gastrointestinal Early Cancer Prevention and Control Centers,Helicobacter pylori Group of the Division of Gastroenterology of the Chinese Medical Association,Chinese Consensus on Management of Gastric Epithelial Precancerous Conditions and Lesions,et al.,2020.Expert consensus on management strategies of precancerous status and precancerous lesions of gastric mucosa in China (2020).Chinese Journal of Digestion,40(11):731-741.]
刘林，范骁辉，唐旭东，2024.胃黏膜炎—癌转化与中医药治疗潜在优势.中国中西医结合杂志，44(9):1146-1152.[LIU L,FAN X H,TANG X D,2024.Exploration on the superiorities of Chinese medicine for treating gastric mucositis inflammation-cancer transformation.Chinese Journal of Integrated Traditional and Western Medicine,44(9):1146-1152.]
马璐萍，左昕，朱炜楷，等，2025.白花蛇舌草可逆转大鼠胃癌前病变胃黏膜上皮间质转化.浙江大学学报(医学版) (2025-04-08)[2025-05-04].http://kns.cnki.net/kcms/detail/33.1248.r.20250408.1104.002.html.[MA L P,ZUO X,ZHU W K,et al.,2025.Scleromitrion diffusum reverses epithelial mesenchymal trans-formation of gastric mucosa in rats with gastricprecancerous lesions.Journal of Zhejiang University(Medical Sciences) (2025-04-08)[2025-05-04].http://kns.cnki.net/kcms/detail/33.1248.r.20250408.1104.002.html.]
马远新，王健，刘春龙，2025.温胃健脾活血汤联合四联法治疗慢性萎缩性胃炎的疗效及对患者胃肠激素、 氧化应激的影响.中药材(2):505-508.[MA Y X,WANG J,LIU C L,2025.Therapeutic effect of Wenwei Jianpi Huoxue decoction combined with quadruple therapy on chronic atrophic gastritis and its influence on gastrointestinal hormones and oxidative stress in patients.China Industrial Economics (2):505-508.]
裴蓓，孙琴，丁文静，等，2025.脾胃培源方治疗脾胃虚弱型慢性萎缩性胃炎伴肠上皮化生随机对照研究.中国中西医结合杂志，45(2):146-152.[PEI B,SUN Q,DING W J,et al.,2025.Treatment of chronic atrophic gastritis with Pi-Wei weakness type accompanied with intestinal Metaplasia by Piwei Peiyuan decoction:a randomized controlled trial.Chinese Journal of Integrated Traditional and Western Medicine,45(2):146-152.]
覃深，唐梅文，唐燕，等，2019.七方胃痛方加减结合西医常规治疗慢性胃炎伴肠化生.吉林中医药，39(8):1069-1072.[QIN S,TANG M W,TANG Y,et al.,2019.Qifang Weitong decoction combined with western medicine in the treatment of chronic gastritis with intestinal Metaplasia.Jilin Journal of Chinese Medicine,39(8):1069-1072.]
全胜源，2017.加味七方胃痛颗粒对胃癌前病变大鼠Ras基因的干预效应，硕士学位论文.南宁：广西中医药大学.(QUAN S Y,2017.Intervention effect of Jiawei Qifang Weitong granule on Ras gene in rats with gastric precance-rous lesions,Thesis for M.S.Nanning:Guangxi University of Chinese Medicine.)
唐旭东，王凤云，李慧臻，等，2019.痞满中医临床实践指南(2018).中医杂志，60(17):1520-1530.[TANG X D,WANG F Y,LI H Z,et al.,2019.Clinical practice guideline for distention and fullness of traditional Chinese medicine(2018).Journal of Traditional Chinese Medicine,60(17):1520-1530.]
田惠芳，唐梅文，陈先翰，等，2016.加味七方胃痛颗粒对慢性萎缩性胃炎大鼠胃黏膜病理形态学的影响.中国中西医结合消化杂志，24(11):839-841.[TIAN H F,TANG M W,CHEN X H,et al.,2016.Influence of modified Qifang Weitong Granules on gastric mucosa in rats with chronic atrophic gastritis at the aspect of pathomorphology.Chinese Journal of Integrated Traditional and Western Medicine on Digestion,24(11):839-841.]
王婷，全胜源，常亮，等，2022.加味七方胃痛颗粒对慢性萎缩性胃炎大鼠MEK基因表达的影响.时珍国医国药，33(5):1032-1035.[WANG T,QUAN S Y,CHANG L,et al.,2022.Effects of Jiawei Qifang Weitong Granules on MEK gene expression in rats with chronic atrophic gastritis.Lishizhen Medicine and Materia Medica Research,33(5):1032-1035.]
魏伟，吴希美，李元建，2010.药理实验方法学.第4版.北京：人民卫生出版社：69-73.[WEI W,WU X M,LI Y J,2010.Experimental Methodology in Pharmacology.4th edition.Beijing:People′s Medical Publishing House:69-73.]
熊常州，陈鑫源，王婷，等，2024.七方胃痛颗粒治疗胃癌的作用机制及信号通路研究进展.中国医药导刊，26(11):1121-1125.[XIONG C Z,CHEN X Y,WANG T,et al.,2024.Research progress on the mechanism of action and signaling pathway of qifangweitong granules in the treatment of gastric cancer.Chinese Journal of Medicinal Guide,26(11):1121-1125.]
熊常州，古文姝，方以峻，等.2025.基于转录组学联合蛋白质组学的加味七方胃痛颗粒抗慢性萎缩性胃炎的作用机制探究.时珍国医国药，36(4):601-608.[XIONG C Z,GU W S,FANG Y J,et al.,2025.Exploring the action mechanism of modified Qifang Weitong Granule against chronic atrophic gastritis based on transcriptomics combined with proteomics.Lishizhen Medicine and Materia Medica Research,36(4):601-608.]
叶芸，李春灵，屈孟琪，等，2025.乐胃饮加味方通过PI3K/AKT/mTOR信号通路调控糖酵解干预慢性萎缩性胃炎.中国中西医结合杂志，45(2):190-197.[YE Y,LI C L,QU M Q,et al.,2025.Modified leweiyin formula regulates glycolysis through PI3K/AKT/mTOR signaling pathway in treatment of chronic atrophic gastritis.Chinese Journal of Integrated Traditional and Western Medicine,45(2):190-197.]
余艳秋，王建宁，翟启智，等，2018.Ki-67、 p53、 P504s在胃癌前病变和早期胃癌中的表达及其意义.胃肠病学，23(10):591-596.[YU Y Q,WANG J N,ZHAI Q Z,et al.,2018.Expressions and significance of Ki-67,p53 and P504s in gastric precancerous lesions and early gastric cancer.Chinese Journal of Gastroenterology,23(10):591-596.]
中国中西医结合学会消化系统疾病专业委员会，2025.慢性萎缩性胃炎中西医结合诊疗专家共识(2025年).中国中西医结合消化杂志，33(3):230-241.[Digestive System Diseases Professional Committee of Chinese Association of Integrative Medicine,2025.Expert consensus on integrated traditional Chinese and western medicine diagnosis and treatment of chronic atrophic gastritis(2025).Chinese Journal of Integrated Traditional and Western Medicine on Digestion,33(3):230-241.]
AL-MOUNDHRI M S,NIRMALA V,AL-HADABI I,et al.,2005.The prognostic significance of p53,p27 kip1,p21 waf1,HER-2/neu,and Ki67 proteins expression in gastric cancer:a clinicopathological and immunohistochemical study of 121 Arab patients.J.Surg.Oncol.,91(4):243-252.
BANKS M,GRAHAM D,JANSEN M,et al.,2019.British so-ciety of gastroenterology guidelines on the diagnosis and mana-gement of patients at risk of gastric adenocarcinoma.Gut,68(9):1545-1575.
CORREA P,PIAZUELO M B.2012.The gastric precancerous cascade.J.Dig.Dis.,13(1):2-9.
DESHPANDE D,CHHUGANI K,CHANG Y T,et al.,2023.RNA-seq data science:from raw data to effective interpretation.Front.Genet.,14:997383.
ISMAEL A T,ABDULHAMEED R A,JALAL J A,et al.,2024.Expression of cytokeratin 7/20 and Ki67 in Helicobacter pylori-associated gastritis and intestinal metaplasia.J.Infect.Dev.Ctries,18(7):1032-1040.
JIA Z J,MEI J,ZHANG Y,et al.,2023.Whole genome methylation combined with RNA-seq reveals the protective effects of Gualou-Xiebai herb pair in foam cells through DNA methylation mediated PI3K-AKT signaling pathway.Front.Immunol.,14:1054014.
LI H Q,ZHENG L Q,ZHONG G D,et al.,2024.Gastric epithelial neoplasm of fundic-gland mucosa lineage:representative of the low atypia differentiated gastric tumor and Ki67 may help in their identification.Pathol.Oncol.Res.,30:1611734.
MORGOS D T,STEFANI C,MIRICESCU D,et al.,2024.Targeting PI3K/AKT/mTOR and MAPK signaling pathways in gastric cancer.Int.J.Mol.Sci.,25(3):1848.
SETHI N,KIKUCHI O,MCFARLAND J,et al.,2019.Mutant p53 induces a hypoxia transcriptional program in gastric and esophageal adenocarcinoma.JCI Insight,4(15):128439.
SHIMIZU T,MARUSAWA H,MATSUMOTO Y,et al.,2014.Accumulation of somatic mutations in TP53 in gastric epithelium with Helicobacter pylori infection.Gastroenterology,147(2):407-417.e3.
SUNG H,FERLAY J,SIEGEL R L,et al.,2021.Global cancer statistics 2020:GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.CA Cancer J.Clin.,71(3):209-249.
TZANAKIS N E,PEROS G,KARAKITSOS P,et al.,2009.Prognostic significance of p53 and Ki67 proteins expression in Greek gastric cancer patients.Acta Chir.Belg.,109(5):606-611.
WANG X,LIU Y Y,ZHAO Q Y,et al.,2024.PILRB poten-tiates the PI3K/AKT signaling pathway and reprograms cholesterol metabolism to drive gastric tumorigenesis and metastasis.Cell Death Dis.,15(9):642.
XU M M,REN L,FAN J H,et al.,2022.Berberine inhibits gastric cancer development and progression by regulating the JAK2/STAT3 pathway and downregulating IL-6.Life Sci.,290:120266.
YANG W J,ZHAO H P,YU Y,et al.,2023.Updates on global epidemiology,risk and prognostic factors of gastric cancer.World J.Gastroenterol.,29(16):2452-2468.
YOUSEFI B,MOHAMMADLOU M,ABDOLLAHI M,et al.,2019.Epigenetic changes in gastric cancer induction by Helicobacter pylori.J.Cell.Physiol.,234(12):21770-21784.
YU S S,CHEN C,CHEN M,et al.,2024.MAGOH promotes gastric cancer progression via hnRNPA1 expression inhibition-mediated RONΔ160/PI3K/AKT signaling pathway activation.J.Exp.Clin.Cancer Res.,43(1):32.
ZHANG S X,TIAN W,LIU Y L,et al.,2022.Mechanism of N-methyl-N-nitroso-urea-induced gastric precancerous lesions in mice.J.Oncol.,2022:3780854.
ZHU Y N,WANG J,WANG J,et al.,2023.Application of serum gastric function markers and digestive tumor indices to the diagnosis of early gastric cancer and precancerous lesions.Saudi Med.J.,44(8):795-800.
基本信息:
DOI：10.13417/j.gab.044.000856
中图分类号:R285.5
引用信息:
[1]熊常州,古文姝,方以峻,等.基于动物实验和转录组学探究加味七方胃痛颗粒阻断大鼠胃“炎癌转化”的作用机制[J].基因组学与应用生物学,2025,44(08):856-868.DOI:10.13417/j.gab.044.000856.
基金信息:
国家自然科学基金项目(82360959); 广西壮族自治区自然科学基金重点项目(2024GXNSFDA010021);广西壮族自治区自然科学基金青年科学基金项目(2024GXNSFBA010160); 广西高校中青年教师科研基础能力提升项目(2023KY0297); 广西研究生教育创新计划项目(YCBZ2025183)共同资助
2025-08-25
2025-08-25