Article(id=1322927224353075757, tenantId=1146029695717560320, journalId=1255847919539208197, issueId=1322926985957221241, articleNumber=null, orderNo=null, doi=10.13193/j.issn.1673-7717.2025.11.035, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=null, receivedDateStr=null, revisedDate=null, revisedDateStr=null, acceptedDate=null, acceptedDateStr=null, onlineDate=1793340029085, onlineDateStr=2026-10-30, pubDate=1762704000000, pubDateStr=2025-11-10, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1793340029085, onlineIssueDateStr=2026-10-30, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1793340029085, creator=13701087609, updateTime=1793340029085, updator=13701087609, issue=Issue{id=1322926985957221241, tenantId=1146029695717560320, journalId=1255847919539208197, year='2025', volume='43', issue='11', pageStart='1', pageEnd='258', issueExtLink='null', onlineDate='null', pubDate='1762704000000', pubDateStr='2025-11-10', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=0, createTime=1793339972247, creator='13701087609', updateTime=1793340743335, updator='13701087609', preIssue=null, nextIssue=null, articleTotal=null, ext={EN=IssueExt(id=1322930220201804556, tenantId=1146029695717560320, journalId=1255847919539208197, issueId=1322926985957221241, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1322930220201804557, tenantId=1146029695717560320, journalId=1255847919539208197, issueId=1322926985957221241, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null, downloadFileDto=null}, startPage=176, endPage=181, ext={EN=ArticleExt(id=1322927224663454254, articleId=1322927224353075757, tenantId=1146029695717560320, journalId=1255847919539208197, language=EN, title=Research Progress on Mechanism of Banxia Xiexin Decoction(半夏泻心汤)in Treatment of Chronic Atrophic Gastritis, columnId=1256183361521967297, journalTitle=Chinese Archives of Traditional Chinese Medicine, columnName=Target on National Project, runingTitle=null, highlight=null, articleAbstract=

Chronic atrophic gastritis(CAG)is a common disease of the digestive system,and its incidence ranks first among various gastric diseases,with epigastric fullness,pain,pantothenic acid,nausea and vomiting as the main clinical manifestations,and the occurrence of this disease is related to Helicobacter pylori(Hp)infection,dietary and environmental factors,autoimmunity,bile reflux,etc.,among which Hp infection is the most. At present,the treatment of CAGin Western medicine is mainly based on the symptomatic treatment of multi-drug combination,although it can achieve certain effects,but the adverse reactions are obvious,and long-term use is easy to develop drug resistance. Traditional Chinese medicine(TCM)has the advantages of multicomponent,multi-target and multi-channel,and has significant efficacy in the prevention and treatment of CAG. This article summarized and sorted out the theoretical basis and mechanism of Banxia Xingxin Decoction in the treatment of CAGby searching and reviewing the relevant literature of CNKI,Wanfang,PubMed and other databases,in order to provide an important reference and theoretical basis for Banxia Xiexin Decoction in the prevention and treatment of CAG.

, authors=Junli WANG1, Yibin CHEN2, authorsList=Junli WANG, Yibin CHEN, authorCompany=null, correspAuthors=Yibin CHEN, authorNote=null, correspAuthorsNote=null, copyrightStatement=null, copyrightOwner=null, extLink=null, articleAbsUrl=null, sourceXml=null, magXml=null, pdfUrl=null, pdf=null, pdfFileSize=null, pdfExtLink=null, richHtmlUrl=null, mobilePdfUrl=null, reviewReport=null, pdfFirstPage=null, abstractGraph=null, abstractGraphContent=null, abstractVideo=null, citation=null, cebUrl=null, magXmlContent=null, mapNumber=null, fund=null), CN=ArticleExt(id=1322927225066107439, articleId=1322927224353075757, tenantId=1146029695717560320, journalId=1255847919539208197, language=CN, title=半夏泻心汤治疗慢性萎缩性胃炎的机制研究进展, columnId=1256183362172142382, journalTitle=中华中医药学刊, columnName=国家项目点击, runingTitle=null, highlight=null, articleAbstract=

慢性萎缩性胃炎(chronic atrophic gastritis,CAG)是消化系统的常见疾病,其发病率在各种胃病中居首位,临床以上腹饱胀、疼痛、泛酸及恶心呕吐等为主要表现,该病的发生与幽门螺杆菌(helicobacter pylori,Hp)感染、饮食和环境因素、自身免疫、胆汁反流等有关,其中以幽门螺杆菌感染者最多。目前西医治疗CAG以多药合用的对症治疗为主,虽能取得一定效果,但不良反应明显,长期使用容易产生耐药性。而中医药具有多组分、多靶点、多通道等优势,在CAG的预防和治疗中疗效显著。通过检索查阅CNKI、万方、PubMed等数据库相关文献,对半夏泻心汤治疗CAG理论基础和作用机制进行归纳与梳理,以期为半夏泻心汤在防治CAG中提供重要的参考和理论依据。

, authors=王军丽1, 陈一斌2, authorsList=王军丽, 陈一斌, authorCompany=null, correspAuthors=陈一斌, authorNote=

王军丽(1999-),女,甘肃天水人,硕士在读,研究方向:脾胃病的中医临床治疗。

, correspAuthorsNote=
陈一斌(1972-),男,福建莆田人,主任医师,硕士研究生导师,学士,研究方向:脾胃病的中医临床治疗。E-mail:。
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王军丽(1999-),女,甘肃天水人,硕士在读,研究方向:脾胃病的中医临床治疗。

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王军丽(1999-),女,甘肃天水人,硕士在读,研究方向:脾胃病的中医临床治疗。

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半夏泻心汤治疗慢性萎缩性胃炎的机制研究进展
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王军丽 1 , 陈一斌 2
中华中医药学刊 | 国家项目点击 2025,43(11): 176-181
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中华中医药学刊 |国家项目点击 2025 , 43 (11) : 176 -181
半夏泻心汤治疗慢性萎缩性胃炎的机制研究进展
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王军丽1, 陈一斌2
作者信息
  • 1.福建中医药大学,福建 福州 350000
  • 2.福建中医药大学附属厦门中医院,福建 厦门 361000
通讯作者:
陈一斌(1972-),男,福建莆田人,主任医师,硕士研究生导师,学士,研究方向:脾胃病的中医临床治疗。E-mail:。
作者简介:

王军丽(1999-),女,甘肃天水人,硕士在读,研究方向:脾胃病的中医临床治疗。

Research Progress on Mechanism of Banxia Xiexin Decoction(半夏泻心汤)in Treatment of Chronic Atrophic Gastritis
Junli WANG1, Yibin CHEN2
Affiliations
  • 1.Fujian University of Traditional Chinese Medicine,Fuzhou 350000,Fujian,China
  • 2.Xiamen Hospital of Traditional Chinese Medicine Affiliated to Fujian University of Chinese Medicine,Xiamen 361000,Fujian,China
出版时间: 2025-11-10 doi: 10.13193/j.issn.1673-7717.2025.11.035
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慢性萎缩性胃炎(chronic atrophic gastritis,CAG)是消化系统的常见疾病,其发病率在各种胃病中居首位,临床以上腹饱胀、疼痛、泛酸及恶心呕吐等为主要表现,该病的发生与幽门螺杆菌(helicobacter pylori,Hp)感染、饮食和环境因素、自身免疫、胆汁反流等有关,其中以幽门螺杆菌感染者最多。目前西医治疗CAG以多药合用的对症治疗为主,虽能取得一定效果,但不良反应明显,长期使用容易产生耐药性。而中医药具有多组分、多靶点、多通道等优势,在CAG的预防和治疗中疗效显著。通过检索查阅CNKI、万方、PubMed等数据库相关文献,对半夏泻心汤治疗CAG理论基础和作用机制进行归纳与梳理,以期为半夏泻心汤在防治CAG中提供重要的参考和理论依据。

半夏泻心汤  /  慢性萎缩性胃炎  /  作用机制  /  综述

Chronic atrophic gastritis(CAG)is a common disease of the digestive system,and its incidence ranks first among various gastric diseases,with epigastric fullness,pain,pantothenic acid,nausea and vomiting as the main clinical manifestations,and the occurrence of this disease is related to Helicobacter pylori(Hp)infection,dietary and environmental factors,autoimmunity,bile reflux,etc.,among which Hp infection is the most. At present,the treatment of CAGin Western medicine is mainly based on the symptomatic treatment of multi-drug combination,although it can achieve certain effects,but the adverse reactions are obvious,and long-term use is easy to develop drug resistance. Traditional Chinese medicine(TCM)has the advantages of multicomponent,multi-target and multi-channel,and has significant efficacy in the prevention and treatment of CAG. This article summarized and sorted out the theoretical basis and mechanism of Banxia Xingxin Decoction in the treatment of CAGby searching and reviewing the relevant literature of CNKI,Wanfang,PubMed and other databases,in order to provide an important reference and theoretical basis for Banxia Xiexin Decoction in the prevention and treatment of CAG.

Banxia Xiexin Decoction(半夏泻心汤)  /  chronic atrophic gastritis  /  mechanism of action  /  review
王军丽, 陈一斌. 半夏泻心汤治疗慢性萎缩性胃炎的机制研究进展. 中华中医药学刊, 2025 , 43 (11) : 176 -181 . DOI: 10.13193/j.issn.1673-7717.2025.11.035
Junli WANG, Yibin CHEN. Research Progress on Mechanism of Banxia Xiexin Decoction(半夏泻心汤)in Treatment of Chronic Atrophic Gastritis[J]. Chinese Archives of Traditional Chinese Medicine, 2025 , 43 (11) : 176 -181 . DOI: 10.13193/j.issn.1673-7717.2025.11.035
慢性萎缩性胃炎(chronic atrophic gastritis,CAG)指胃黏膜反复受损致固有腺体减少甚至消失,或伴肠腺化生和假幽门腺化生为特征的慢性消化系统疾病[1],发病率随着年龄的增长而升高[2],其发病与幽门螺杆菌(helicobacter pylori,Hp)感染、饮食习惯、环境条件、自身免疫反应、胆汁反流等因素密切相关,目前认为Hp感染是其最主要的发病原因,文献报道Hp阳性患者发生CAG的风险比Hp阴性患者高2.4倍[3]。如果不及时治疗,CAG可能会进展为胃癌(gastric carcinoma,GC),常给患者精神和健康带来严重影响。西医主要以根除Hp、保护胃黏膜以及促进胃肠动力等对症治疗为主,多药合用,虽能取得良好疗效,但会增加药物的不良反应,而且长期使用容易产生耐药性,不能从根本上改善患者的生活质量。中医药在CAG的治疗过程中具有疗效突出,不良反应少等优势。仲景名方半夏泻心汤原为治疗寒热错杂之痞证而设,近年来国内外研究发现,半夏泻心汤可以通过多种途径治疗CAG,基于此,该综述总结了近年来半夏泻心汤治疗CAG的理论基础和作用机制,以期为临床治疗CAG提供重要的参考。
CAG中医古籍未载其名,然观其症,可将之归属于中医学“胃脘痛、痞满、呕吐、嘈杂”等范畴。CAG的发生,多由气滞、寒凝、热郁、湿阻、血瘀等损伤脾胃,导致脾胃升降失司,即出现胃痛,痞满之象,日久则脾胃虚弱,易招致病邪内侵,故容易形成虚实夹杂,寒热错杂之证。可见,脾胃升降失司是CAG的核心病机,寒热错杂是其重要的病理表现,故CAG的治疗宜调理脾胃升降,平调寒热。《类证治裁·痞满》谓:“痞虽虚邪,然表气入里,热郁于心胸之分,必用苦寒为泻,辛甘为散,诸泻心汤所以寒热共用也”,指出可以用泻心汤类平调寒热。
半夏泻心汤首次出现于《伤寒论》中,本为少阳证误下后,邪陷心下,胃气呆滞,湿浊壅聚,而出现呕吐,肠鸣,下利之痞证所设。该方由半夏、黄连、干姜、人参、炙甘草、黄芩、大枣七味药组成。方中半夏燥湿化痰,和胃降逆消痞。黄芩黄连苦寒泻热。干姜辛温暖脾化饮,与芩、连相配伍,辛开苦降,宣降结气以消痞。人参、大枣、甘草补中,以复脾升胃降之职。诸药共奏辛开苦降,和胃消痞之功。作为辛开苦降之代表方,临床上主要用于治疗寒热错杂之消化系统疾病,如慢性胃炎、溃疡性结肠炎等,其中在CAG的治疗中最为常见。
现代药理学研究证实,半夏泻心汤主要通过其有效化学成分发挥治疗作用。其中半夏中的半夏多糖、生物碱、β-谷甾醇等均有一定的抗氧化活性,半夏多糖还具有抗肿瘤的作用[4]。李泽森等[5]发现干姜可上调小鼠超氧化物歧化酶(Superoxide dismutase,SOD)水平及抑制促炎细胞因子白细胞介素(interleukin,IL)-6的表达,减弱氧化应激和炎症反应。黄芩苷可以激活相关信号通路发挥抗氧化作用[6]。人参皂苷可以提高调节免疫蛋白IgG、IgA、IgM水平,抑制成纤维细胞生长因子(basic fibrobiast growth factor,bFGF)蛋白表达,提高CAG大鼠免疫功能,降低炎症水平[7]。大枣多糖可提高机体免疫功能[8]。甘草酸通过降低血清肿瘤坏死因子-α(tumor necrosis factor,TNF-α)的含量来减轻胃黏膜的炎症反应[9]。黄连素、黄芩素可以抑制促炎细胞因子的表达,抑制炎症反应,保护胃黏膜[10-11]。此外,黄连碱、小檗碱能抑制脲酶活性,抑制Hp,从而发挥治疗CAG的作用[12]。也有研究证实,甘草酸、人参皂苷、黄连碱具有促细胞凋亡的作用,可以延缓CAG发展为GC的进程[13]。综上,通过对半夏泻心汤方证基础和药理作用分析,均为半夏泻心汤治疗CAG提供了坚实的理论基础。
炎症是一个复杂的过程,涉及各种不同的细胞和多种分子。既往研究表明,胃癌前病变(precancerous lesions of gastric cancer,PLGC)与全身炎症细胞因子(比如IL-6、IL-8、IL-10、IL-1β、IL-17等)及TNF-α之间有着密切的关联[14]。相关文献报道,IL-8基因的遗传多态性会影响泌酸性CAG和GC严重程度[15]。IL-10、IL-1β及TNF-α会增加Hp感染的风险,从而更易导致CAG及GC的发生[16]。IL-6、IL-17在胃黏膜组织中的表达与炎症程度呈正相关,胃黏膜中的持续炎症反应被认为是CAG发展为胃癌的初始驱动因素[17]。有研究表明,单独使用选择性环氧化酶-2(cyclooxygenase-2,COX-2)抑制剂塞来昔布治疗CAG可以起到有益的效果[18]。因此,抑制胃黏膜的炎症反应对于防治CAG及延缓其向GC的转变可能起着重要作用。
钮国英[19]探究半夏泻心汤加减治疗Hp相关性胃炎的疗效及其对胃蛋白酶原I(Pepsinogen,PGI)、TNF-α的影响,结果发现,半夏泻心汤加减联合三联疗法总有效率高于单纯三联疗法,且可以降低TNF-α、PGⅠ水平,减少炎性因子释放,从而加快胃黏膜功能的恢复。李晶等[20]通过研究发现,半夏泻心汤可以降低IL-6、C反应蛋白(C-reactiveprotein,CRP)等因子水平。李慧臻等[21]发现半夏泻心汤及四联杀菌法可通过调控趋化因子配体9[Chemokine(C-X-Cmotif)ligand 9,CXCL9]、CXCL10,降低炎性因子IL-17A、IL-6、IL-22表达,发挥治疗CAG的作用。综上所述,半夏泻心汤显示出良好的抗炎活性,对于CAG的治疗起到关键作用。
CAG的发病机制十分复杂,目前尚未完全明确,但既往研究发现,其与胃黏膜免疫功能有着密切的关系[22]。胃黏膜免疫系统是人体免疫系统的重要组成部分,它通过先天免疫和适应性免疫来执行其免疫功能。一方面,当细菌和病毒等病原体入侵胃黏膜时,上皮细胞和先天免疫细胞会通过物理、化学和生物过程进行防御。另一方面,免疫细胞分泌的白细胞介素和趋化因子等细胞因子通过抗原呈递帮助T细胞和B细胞等淋巴细胞呈递抗原,进一步触发适应性免疫的发生[23]。有研究报道,在CAG中,CD4+T细胞会攻击壁细胞,导致壁细胞和主细胞丢失,最终导致黏膜萎缩和缺乏[24],而调节免疫细胞(如嗜酸性粒细胞、M2巨噬细胞、肥大细胞等)的下游募集和激活可减少CAG的发生[6]。Hp感染可通过诱导先天免疫和适应性免疫,导致胃组织损伤。因此,维持胃黏膜的免疫平衡对于防治CAG可能具有重要意义。
李慧臻等[25]通过动物实验发现,半夏泻心汤可通过干预相关细胞因子的表达,调节调节性T细胞(regulatory T cells,Treg)/辅助性T细胞17(T helper cell 17,Th17)的免疫失衡,从而改善胃黏膜的免疫微环境,进而治疗CAG。邓谦等[26]选取160例脾胃湿热型CAG患者作为研究对象,探讨半夏泻心汤加减对脾胃湿热型慢性萎缩性胃炎患者免疫功能与炎性因子水平的影响,结果表明,半夏泻心汤加减能显著提高CAG患者的CD3+、CD4+百分比及CD4+/CD8+比值,降低CD8+百分比,血清IL-2、IL-6、TNF-α水平,从而提高脾胃湿热型患者的临床疗效与免疫功能,降低机体炎症反应,进而缓解胃痛,恶心呕吐等临床症状。结合以上研究,表明半夏泻心汤可以通过调节胃黏膜免疫功能,从而保护胃黏膜,达到有效治疗CAG的作用。
胃上皮细胞通过维持细胞增殖和凋亡之间的平衡来维持生理过程。细胞凋亡的发生受到细胞内凋亡调节蛋白的调控,在已知的凋亡调节蛋白中,B 淋巴细胞瘤2(B-cell lymphoma-2,Bcl-2)家族蛋白发挥着细胞凋亡“主开关”的作用,Bcl-2为抗细胞凋亡的因子,Bcl-2相关X蛋白基因(Bcl-2 associated X protein,Bax)为促进细胞凋亡发生的因子[27]。Bax的表达与CAG症状的严重程度成正相关,而Bcl-2的表达下降,会增加异常细胞数目,使CAG病情趋向恶变[28]。此外,半胱氨酸蛋白酶-3(cysteine aspartate-specific protease 3,Caspase-3)在执行细胞凋亡和促进创伤愈合的过程中发挥着重要的作用[29]。因此,了解胃上皮细胞的增殖和凋亡的平衡对于防治CAG的发生及向GC的转变起着关键作用。
有研究表明半夏泻心汤可以通过调控有关信号通路来抑制胃黏膜上皮层细胞和固有层细胞的增殖并加速其凋亡,从而阻止胃黏膜的细胞发生突变[30]。此外,刘余等[31]研究证实半夏泻心汤可通过上调胃黏膜中Bcl-2mRNA表达,下调活化的凋亡执行因子Caspase-3的表达,抑制胃黏膜上皮细胞的过度凋亡,从而抵抗胃黏膜的应激性损伤。同时,符娇文等[32]采用MNNG结合情志刺激、饥饱失常法造模,观察大鼠一般状况、胃黏膜病理状况和表皮生长因子受体(epidermal growth factor receptor,EGFR)、Bcl-2蛋白表达情况,结果发现,半夏泻心汤组的体质量高于生理盐水组,大鼠机体黏膜没有萎缩,有明显的保护作用,半夏泻心汤组大鼠EGFR、Bcl-2蛋白表达量及表达率均低于生理盐水组,以此来诱使胃黏膜“病态”细胞凋亡,使细胞增殖和凋亡恢复平衡。综上,半夏泻心汤对于维持胃上皮细胞增殖和凋亡的平衡有重要作用。
Hp是I类致癌物,Hp感染为CAG最常见的病因[33]。有研究表明,Hp感染后,其毒力因子细胞毒素相关蛋白A(cytotoxin-associated protein A,CagA)与上皮细胞受体结合并刺激不同的信号通路,从而破坏胃上皮细胞的屏障。此外,Hp释放的酶(即脲酶、磷脂酶)和空泡毒素相关蛋白A(Vacuolating cytotoxin A,VacA)会损害胃黏膜,并刺激炎症和免疫反应,会导致胃上皮细胞发生凋亡[34]。因此根除Hp是治疗CAG的重要方法之一。西药根除Hp主要采用四联疗法,但是由于不良反应大,耐药性等问题未能取得良好的疗效。因此近年来中医药已成为一种有前途的辅助根除Hp的替代疗法。
既往研究表明,中药黄连、半夏、甘草、黄芩、丹参、陈皮、柴胡、木香、枳实、广藿香等具有明显的抑菌或杀菌作用[35-37]。刘紫薇[38]通过研究发现,半夏泻心汤加减联合四联治疗Hp相关性CAG,与对照组(单纯四联疗法)相比可明显提高Hp根除率,且在胃脘痛、胃脘灼热、口苦等临床症状的改善方面也优于对照组。同时有研究发现,加味半夏泻心汤可能通过降低CagA、VacA水平,上调PG-Ⅰ、PG-Ⅱ水平,来辅助根除CAG患者所感染的Hp,改善胃黏膜功能[39]。综上,半夏泻心汤在辅助根除Hp方面有明确的疗效。
氧化应激是体内氧化与抗氧化作用失衡的一种状态。基础浓度的活性氧(reactive oxygen species,ROS)对于细胞功能的表现是不可或缺的,而过量的活性氧会对DNA、脂质和蛋白质等细胞大分子造成损害,最终导致坏死和细胞凋亡。既往研究发现,当体内自由基增多时,细胞受到氧化作用,会形成多种过氧化产物,丙二醛(malonaldehyde,MDA)即是其中的代表。血清超氧化物歧化酶(SOD)是唯一可以消除ROS的酶,是防御氧化应激的关键成分[40]。有研究指出,CAG大鼠胃黏膜组织存在着氧化应激损伤[41]。Hp感染会通过产生ROS直接引起胃上皮细胞的氧化应激[42]。因此,减轻氧化应激可能对于保护胃黏膜及防治CAG有重要意义。
马会妙等[43]通过临床研究发现,半夏泻心汤可以降低MDA、IL-6、TNF-α水平,上调超氧化物歧化酶(SOD)水平,减轻氧化应激反应和炎症反应,从而保护胃黏膜,进一步达到治疗CAG的作用。石铖等[44]通过大鼠试验研究发现,半夏泻心汤可以通过维持氧化-抗氧化平衡来治疗CAG,尤其以高剂量组作用明显。
转录因子叉头框蛋白P3(forkhead box protein P3,FoxP3)是调节性T细胞(Treg)的重要调节因子[45]。Treg细胞可以通过分泌白细胞介素-10、转化生长因子-β(Transforming growth factor-β,TGF-β)等免疫细胞因子间接发挥免疫抑制作用[46-47]。此外,Treg细胞上的淋巴细胞活化基因(lymphocyte-activation gene-3,LAG-3)也可与未成熟树突状细胞上的主要组织相容性复合体Ⅱ(major histocompatibility complex,MHC-Ⅱ)直接接触来发挥免疫抑制的作用[48]。维甲酸受体相关孤儿受体γt(retinoid-related orphan nuclear receptorγt,RORγt)可以调控Th17的分化,而Th17能控制炎性因子IL-17的产生介导免疫炎症反应[47]。综上,FoxP3通过调控Treg介导免疫抑制,RORγt通过调控Th17介导免疫炎性反应,两者作用相反,处于动态平衡,二者失衡则导致机体免疫力和抗炎能力下降,引发各种炎症性疾病[49]。既往研究表明,胃黏膜组织的炎症程度与IL-17、IL-6等因子的表达与呈正相关,且Hp感染性CAG与FoxP3、RORγt关系的失衡联系密切[17]。因此,FoxP3/RORγ信号通路的平衡状态对维持胃黏膜稳态具有重要意义。
韦玉娜等[50]通过造模,研究半夏泻心汤对CAG的作用机制,研究发现,胃黏膜固有层腺体数量不同程度增加,凋亡细胞减少,尤其以低剂量组改善最为明显,干预可能与其下调大鼠胃黏膜Foxp3、RoRγt的mRNA表达及相关细胞因子的表达有关。此外,吴忠祥等[51]发现半夏泻心汤及其拆方还可通过下调血清中IFN-γ[受转化生长因子-β(transforming growth factor-β,TGF-β)的调控]的表达,调节细胞免疫来发挥保护胃黏膜的作用。
Janus激酶2(recombinant janus kinase 2,JAK2)信号转导和转录激活因子3(signal transducer and activator of transcription 3,STAT3)信号通路与癌症、炎症和免疫有关,是一条应用十分广泛的通路。50多种不同的前细胞因子受体会引起JAK2/STAT3的异常激活。当前细胞因子与其受体结合,JAK2就通过转磷酸化诱导其自身激活,一旦被激活,JAK2就会磷酸化特定酪氨酸上受体的细胞内尾部,这些尾部反过来充当转录因子STAT家族成员的对接位点[52]。CAG发展到后期可能进展为GC,既往文献报道,在GC中,JAK2/STAT3信号通路被异常激活后会促进肿瘤细胞的增殖[53]。JAK2/STAT3信号通路也是目前发现的炎症通路之一,当该通路被激活时可促进巨噬细胞释放TNF-α、IL-1β、IL-6等炎症因子[54]。有研究表明JAK抑制剂通过防止JAK蛋白磷酸化,从而减弱细胞内信号传导,其多在炎症性疾病中应用[55]。因此,抑制JAK2/STAT3信号通路的激活,对于CAG的防治及CG的发生可能有着重要意义。
研究发现,黄芪甲苷、人参皂苷可能通过抑制JAK2/STAT3信号通路的激活,减轻炎症反应,提高免疫功能,保护胃炎小鼠的胃黏膜[56-57]。此外,董利洋等[58]发现,半夏泻心汤可以明显降低炎症因子TNF-α、IL-1β、IL-6、MDA水平,同时上调Bax等基因的表达,下调Bcl-2基因的表达,从而抑制JAK2、STAT3的磷酸化,促进细胞凋亡,来达到治疗CAG的目的。
无翼样糖蛋白(winglessintegrated,Wnt)是富含半胱氨酸的糖蛋白,具有调节关键的细胞功能,包括增殖、分化、细胞凋亡等。β-连环蛋白(β-catenin)主要通过积聚在细胞-细胞接触位点,促进细胞间的黏附[59]。在Wnt/β-catenin信号通路未激活时,β-catenin的破坏复合物会磷酸化β-连环素,随后发生降解。当通路被激活时,会抑制糖原合成酶激酶-3β(glycogen synthase kinase-3β,GSK-3β)的活性,阻止下游分子的磷酸化,使β-catenin与细胞核中的相应受体结合,随后促进细胞增殖[60]。既往研究表明,Wnt信号通路在调节正常胃黏膜的增殖、干细胞维持和稳态中起着至关重要的作用[61]。异常激活的Wnt/β-catenin信号通路会引起β-catenin在细胞核内明显累积,上皮细胞异常增殖,引起CAG的发生[62]。此外,Wnt/β-catenin信号通路的传导也可以触发Bax/Bcl-2、TRAIL及Fasc的启动来促进细胞凋亡,从而抑制癌症细胞的生长[63]。贾子琴等[64]通过动物试验发现,Wnt/β-catenin信号转导通路异常活化参与胃炎的病理进程。又有研究发现,Hp感染并发癌前病变的患者胃肠组织中β-catenin呈现高表达状态,Wnt/β-catenin信号通路的作用可能成为治疗CAG的有前途的方式。
李灵[65]通过动物实验探究半夏泻心汤对慢性萎缩性胃炎大鼠Wnt/β-catenin信号通路的影响,结果发现,半夏泻心汤可以通过抑制Wnt/β-catenin信号通路的异常激活,从而抑制胃黏膜上皮层细胞和固有层细胞的增殖并加速其凋亡,进而阻止CAG的进一步发展,且在病理改变方面,高剂量组效果更优。
PI3k/AKT/mTOR信号通路在调节信号转导和细胞增殖、凋亡、代谢和血管生成等生物过程中发挥重要作用[66]。当受到某种刺激时,磷脂酰肌醇3-激酶(phosphatidylinositol3-kinase,PI3k)被激活,进而产生第二信使磷脂酰肌醇3,4,5-三磷酸(phosphatidylinositol-3,4,5-triphosphate,PIP3),PIP3随后募集并激活细胞质中的苏氨酸蛋白激酶B(protein kinase B,PKB/AKT),从而使哺乳动物雷帕霉素靶蛋白(mammaliantargetofrapamycin,mTOR)的活性增加,影响着细胞的代谢。AKT磷酸化参与细胞代谢和凋亡的多个下游靶点,如激活Bcl-2相关细胞死亡激动剂(BAD)从而加速细胞凋亡,来阻止肿瘤细胞的过度增殖。AKT包含3种亚型AKT1、AKT2和AKT3,既往研究表明,AKT1在(包括胃在内的)许多组织中广泛表达[67]。因此,PI3K/AKT信号通路在CAG的防治中可能具有重要的意义。
刘嘉诚等[68]通过动物实验发现中药半夏泻心汤通过影响PLGC大鼠胃黏膜组织微环境变化的3个关键环节,即PI3K/Akt/mTOR信号通路中的启动子、调控器及效应子,从而影响并阻断PLGC的发生发展。此外,门凯龙[30]通过研究发现半夏泻心汤可以通过抑制PI3K/AKT细胞信号转导通路来抑制胃黏膜上皮层细胞和固有层细胞的增殖并加速其凋亡,从而阻止胃黏膜上皮层细胞和固有层细胞发生突变,高剂量半夏泻心汤在抑制PI3K/AKT通路方面优于低剂量组,还可以抑制胃黏膜的炎性反应,从而减少其萎缩。又有研究证实,黄芩苷可以激活磷脂酰肌醇3-激酶/蛋白激酶B(PI3K/Akt)通路发挥抗氧化作用,也可降低促凋亡蛋白半胱氨酸蛋白酶-3(Caspase-3)的表达,缓解细胞损伤[6]。
CAG是消化系统的常见病,由于其发病周期长,易反复及并发症多,常给患者精神和健康带来严重影响。由于西药治疗的不良反应及耐药性等问题,未能取得满意的疗效。近年来,中医药疗法在临床中有着广阔的应用前景,而且在CAG的防治方面取得了显著进展。基于此,此文通过检索查阅近年来数据库文献,总结和归纳了经典名方半夏泻心汤治疗CAG的相关机制,主要通过抑制炎症反应、调节免疫功能、调控细胞增殖与凋亡、辅助根除幽门螺杆菌、抗氧化应激和调控CAG相关信号通路等途径,发挥对CAG的预防和治疗作用,具有多成分-多靶点-多途径的特点。
虽然半夏泻心汤在CAG的治疗方面已经有一定的研究和应用,但是由于中药成分比较复杂,CAG的发病机制又多样,所以该研究仍面临一些问题及挑战。首先,在理论基础研究方面,虽然药理学研究证实半夏泻心汤中许多中药的活性成分对于CAG的治疗有效,但其中有效的化学成分尚未在临床中推广应用,且各活性成分之间的作用关系也不清楚。其次,现有研究无论是临床试验还是动物实验,仍然存在样本量小等问题。此外,在分子学研究方面,对于有关分子靶点的作用机制研究仍然不够全面,且由于各途径之间的关系尚不清楚。因此,未来的研究应从药物与临床紧密结合出发,选择科学的研究方法,对有关分子途径进行重点、多方面的研究,这对明确半夏泻心汤治疗CAG的机制具有重要意义。
  • 国家中医药管理局吴耀南全国名老中医药专家传承工作室项目(国中医药人教函〔2022〕75号)
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doi: 10.13193/j.issn.1673-7717.2025.11.035
  • 首发时间:2026-10-30
  • 出版时间:2025-11-10
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国家中医药管理局吴耀南全国名老中医药专家传承工作室项目(国中医药人教函〔2022〕75号)
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    1.福建中医药大学,福建 福州 350000
    2.福建中医药大学附属厦门中医院,福建 厦门 361000

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陈一斌(1972-),男,福建莆田人,主任医师,硕士研究生导师,学士,研究方向:脾胃病的中医临床治疗。E-mail:。
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鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
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