Article(id=1322923761376305903, tenantId=1146029695717560320, journalId=1255847919539208197, issueId=1322923490592043032, articleNumber=null, orderNo=null, doi=10.13193/j.issn.1673-7717.2025.05.027, 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=1793339203446, onlineDateStr=2026-10-30, pubDate=1746806400000, pubDateStr=2025-05-10, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1793339203446, onlineIssueDateStr=2026-10-30, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1793339203446, creator=13701087609, updateTime=1793339203446, updator=13701087609, issue=Issue{id=1322923490592043032, tenantId=1146029695717560320, journalId=1255847919539208197, year='2025', volume='43', issue='5', pageStart='1', pageEnd='258', issueExtLink='null', onlineDate='null', pubDate='1746806400000', pubDateStr='2025-05-10', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=0, createTime=1793339138887, creator='13701087609', updateTime=1793340572227, updator='13701087609', preIssue=null, nextIssue=null, articleTotal=null, ext={EN=IssueExt(id=1322929502539612595, tenantId=1146029695717560320, journalId=1255847919539208197, issueId=1322923490592043032, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1322929502539612596, tenantId=1146029695717560320, journalId=1255847919539208197, issueId=1322923490592043032, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null, downloadFileDto=null}, startPage=139, endPage=143, ext={EN=ArticleExt(id=1322923763125330672, articleId=1322923761376305903, tenantId=1146029695717560320, journalId=1255847919539208197, language=EN, title=Clinical Application of Huangqin Decoction(黄芩汤)in Digestive System Disease and Research Progress of Its Anti-Inflammatory Mechanism, columnId=1256183361521967297, journalTitle=Chinese Archives of Traditional Chinese Medicine, columnName=Target on National Project, runingTitle=null, highlight=null, articleAbstract=

Digestive system diseases are a common type of diseases in clinical practice,and the characteristics of these diseases are complex and related. Traditional Chinese medicine is guided by the concept of“holistic concept”and“syndrome differentiation and treatment”,which has the advantages of high safety,good efficacy and small adverse reactions in the treatment of digestive diseases. Huangqin Decoction(黄芩汤,HQD),originated from the ancestor of the formula book Treatiseon Miscellaneous Diseases of The Typhoid Fever,has been widely used in digestive system diseases because of its multiple pharmacological effects. Through reviewing the clinical application of HQD and experimental research literature,the author has found that HQD can regulate multiple signaling pathways to achieve anti-inflammatory effects. HQD can regulate inflammation-related signals such as JAK/STAT-related signaling pathway,MAPK related signaling pathway and NF-κB-related signaling pathway,as well as macrophage phenotypic changes to play an anti-inflammatory role,and the use of the above pathways can reduce the levels of pro-inflammatory factors in the serum in order to achieve the anti-inflammatory effect of the formula. The unique anti-inflammatory advantages of HQD are widely used in digestive system diseases,because the inflammatory environment of the human body plays an important role in the“inflammation-cancer transformation”in the process of disease development. Therefore,the formula is commonly used in the treatment of inflammatory diseases such as ulcerative colitis,primary hepatocellular carcinoma,gastric carcinoma,acute enteritis and other inflammatory diseases in the clinic. Therefore,this article summarized the anti-inflammatory effect and clinical application of HQD,with a view to providing reference and ideas for the expansion of clinical application and further in-depth study of this formula.

, authors=Pengliang LIU1, Erping XU1, 2, Nan ZHANG1, Mingyuan ZHANG3, Lijie KANG4, Hexuan LIU1, Fushan MENG1, authorsList=Pengliang LIU, Erping XU, Nan ZHANG, Mingyuan ZHANG, Lijie KANG, Hexuan LIU, Fushan MENG, authorCompany=null, correspAuthors=Erping XU, Nan ZHANG, 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=1322923763779642097, articleId=1322923761376305903, tenantId=1146029695717560320, journalId=1255847919539208197, language=CN, title=黄芩汤在消化系统疾病中的临床应用及其抗炎机制研究进展, columnId=1256183362172142382, journalTitle=中华中医药学刊, columnName=国家项目点击, runingTitle=null, highlight=null, articleAbstract=

消化系统疾病是临床上常见的一类疾病,该系统疾病具有症状复杂且关联性强的特点。中医以“整体观念”“辨证论治”为指导思想,在消化系统疾病的治疗中具有安全性高、疗效好以及不良反应小等优势。黄芩汤源于方书之祖《伤寒杂病论》,具有清热止痢、和中止痛之功,因其具有多种药理作用而广泛应用于消化系统疾病当中。通过查阅黄芩汤的临床应用和实验研究文献总结发现黄芩汤可通过调节多条信号通路从而达到抗炎的效果。黄芩汤可以通过调控Janus激酶/信号转导及转录激活因子(Janus Kinase/signal transducer and activator transcription,JAK/STAT)相关信号通路、丝裂原活化蛋白激酶(Mitogen-activated protein kinases,MAPK)相关信号通路和核因子-κB(Nuclear factor kappa B,NF-κB)相关信号通路等炎症相关信号以及调节巨噬细胞的表型转变以发挥抗炎作用,利用上述途径可有效减少血清中促炎因子含量。黄芩汤独特的抗炎优势在消化系统疾病中应用广泛,因人体炎症环境对疾病发展过程中“炎-癌转化”有着重要作用,因此该方在临床上常用于治疗腹泻、溃疡性结肠炎和急性肠炎等炎性疾病以及原发性肝癌、胃癌等癌症。就黄芩汤的抗炎作用和临床应用进行综述,以期为该方在临床的扩展应用和进一步的深入研究提供借鉴与思路。

, authors=刘朋良1, 许二平1, 2, 张楠1, 张明远3, 康丽杰4, 刘贺轩1, 孟富山1, authorsList=刘朋良, 许二平, 张楠, 张明远, 康丽杰, 刘贺轩, 孟富山, authorCompany=null, correspAuthors=许二平, 张楠, authorNote=

刘朋良(1997-),男,河南禹州人,硕士在读,研究方向:方剂配伍规律及作用机理规律。

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张楠(1989-),女,河南南阳人,副教授,博士,研究方向:方剂配伍及作用机理规律。E-mali:。
许二平(1962-),男,河南鄢陵人,教授,博士研究生导师,博士,研究方向:方剂配伍及作用机理规律。E-mail:。
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刘朋良(1997-),男,河南禹州人,硕士在读,研究方向:方剂配伍规律及作用机理规律。

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黄芩汤在消化系统疾病中的临床应用及其抗炎机制研究进展
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刘朋良 1 , 许二平 1, 2 , 张楠 1 , 张明远 3 , 康丽杰 4 , 刘贺轩 1 , 孟富山 1
中华中医药学刊 | 国家项目点击 2025,43(5): 139-143
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中华中医药学刊 |国家项目点击 2025 , 43 (5) : 139 -143
黄芩汤在消化系统疾病中的临床应用及其抗炎机制研究进展
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刘朋良1, 许二平1, 2 , 张楠1 , 张明远3, 康丽杰4, 刘贺轩1, 孟富山1
作者信息
  • 1.河南中医药大学中医学院,河南 郑州 450046
  • 2.河南省豫药全产业链研发河南省协同创新中心,河南 郑州 450046
  • 3.河南中医药大学中医药科学院,河南 郑州 450046
  • 4.河南省中医院,河南中医药大学第二附属医院,河南 郑州 450046
通讯作者:
张楠(1989-),女,河南南阳人,副教授,博士,研究方向:方剂配伍及作用机理规律。E-mali:。
许二平(1962-),男,河南鄢陵人,教授,博士研究生导师,博士,研究方向:方剂配伍及作用机理规律。E-mail:。
作者简介:

刘朋良(1997-),男,河南禹州人,硕士在读,研究方向:方剂配伍规律及作用机理规律。

Clinical Application of Huangqin Decoction(黄芩汤)in Digestive System Disease and Research Progress of Its Anti-Inflammatory Mechanism
Pengliang LIU1, Erping XU1, 2 , Nan ZHANG1 , Mingyuan ZHANG3, Lijie KANG4, Hexuan LIU1, Fushan MENG1
Affiliations
  • 1.School of Traditional Chinese Medicine,Henan University of Chinese Medicine,Zhengzhou 450046,Henan,China
  • 2.Collaborative Innovation Center of Research and Development on the Whole Industry Chain of Yu-Yao,Zhengzhou 450046,Henan,China
  • 3.Academy of Traditional Chinese Medicine,Henan University of Chinese Medicine,Zhengzhou 450046,Henan,China
  • 4.Henan Provincial Hospital of Traditional Chinese Medicine,The Second Affiliated Hospital to Henan University of Chinese Medicine,Zhengzhou 450046,Henan,China
出版时间: 2025-05-10 doi: 10.13193/j.issn.1673-7717.2025.05.027
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消化系统疾病是临床上常见的一类疾病,该系统疾病具有症状复杂且关联性强的特点。中医以“整体观念”“辨证论治”为指导思想,在消化系统疾病的治疗中具有安全性高、疗效好以及不良反应小等优势。黄芩汤源于方书之祖《伤寒杂病论》,具有清热止痢、和中止痛之功,因其具有多种药理作用而广泛应用于消化系统疾病当中。通过查阅黄芩汤的临床应用和实验研究文献总结发现黄芩汤可通过调节多条信号通路从而达到抗炎的效果。黄芩汤可以通过调控Janus激酶/信号转导及转录激活因子(Janus Kinase/signal transducer and activator transcription,JAK/STAT)相关信号通路、丝裂原活化蛋白激酶(Mitogen-activated protein kinases,MAPK)相关信号通路和核因子-κB(Nuclear factor kappa B,NF-κB)相关信号通路等炎症相关信号以及调节巨噬细胞的表型转变以发挥抗炎作用,利用上述途径可有效减少血清中促炎因子含量。黄芩汤独特的抗炎优势在消化系统疾病中应用广泛,因人体炎症环境对疾病发展过程中“炎-癌转化”有着重要作用,因此该方在临床上常用于治疗腹泻、溃疡性结肠炎和急性肠炎等炎性疾病以及原发性肝癌、胃癌等癌症。就黄芩汤的抗炎作用和临床应用进行综述,以期为该方在临床的扩展应用和进一步的深入研究提供借鉴与思路。

黄芩汤  /  消化系统疾病  /  临床应用  /  抗炎作用  /  综述

Digestive system diseases are a common type of diseases in clinical practice,and the characteristics of these diseases are complex and related. Traditional Chinese medicine is guided by the concept of“holistic concept”and“syndrome differentiation and treatment”,which has the advantages of high safety,good efficacy and small adverse reactions in the treatment of digestive diseases. Huangqin Decoction(黄芩汤,HQD),originated from the ancestor of the formula book Treatiseon Miscellaneous Diseases of The Typhoid Fever,has been widely used in digestive system diseases because of its multiple pharmacological effects. Through reviewing the clinical application of HQD and experimental research literature,the author has found that HQD can regulate multiple signaling pathways to achieve anti-inflammatory effects. HQD can regulate inflammation-related signals such as JAK/STAT-related signaling pathway,MAPK related signaling pathway and NF-κB-related signaling pathway,as well as macrophage phenotypic changes to play an anti-inflammatory role,and the use of the above pathways can reduce the levels of pro-inflammatory factors in the serum in order to achieve the anti-inflammatory effect of the formula. The unique anti-inflammatory advantages of HQD are widely used in digestive system diseases,because the inflammatory environment of the human body plays an important role in the“inflammation-cancer transformation”in the process of disease development. Therefore,the formula is commonly used in the treatment of inflammatory diseases such as ulcerative colitis,primary hepatocellular carcinoma,gastric carcinoma,acute enteritis and other inflammatory diseases in the clinic. Therefore,this article summarized the anti-inflammatory effect and clinical application of HQD,with a view to providing reference and ideas for the expansion of clinical application and further in-depth study of this formula.

Huangqin Decoction(黄芩汤)  /  digestive diseases  /  clinical applications  /  anti-inflammatory effects  /  review
刘朋良, 许二平, 张楠, 张明远, 康丽杰, 刘贺轩, 孟富山. 黄芩汤在消化系统疾病中的临床应用及其抗炎机制研究进展. 中华中医药学刊, 2025 , 43 (5) : 139 -143 . DOI: 10.13193/j.issn.1673-7717.2025.05.027
Pengliang LIU, Erping XU, Nan ZHANG, Mingyuan ZHANG, Lijie KANG, Hexuan LIU, Fushan MENG. Clinical Application of Huangqin Decoction(黄芩汤)in Digestive System Disease and Research Progress of Its Anti-Inflammatory Mechanism[J]. Chinese Archives of Traditional Chinese Medicine, 2025 , 43 (5) : 139 -143 . DOI: 10.13193/j.issn.1673-7717.2025.05.027
消化系统疾病是临床最常见的一类疾病,临床症状表现复杂且相互关联,在我国有着极高的发病率,有研究显示,消化系统疾病在我国两周发病率约为1.5%,从2012年我国消化系统疾病患病人数表现出逐年上升趋势[1-2]。因此,消化系统疾病的防治对减轻我国医疗负担有着重要意义。中医治疗消化系统疾病有着独有的优势,其“整体观念”和“辨证论治”的思想对于疾病的治疗有着重要的治疗意义[3-4]。黄芩汤始载于《伤寒杂病论》,主治太阳少阳合病,两阳合病致使阳盛而阴虚,阳气下陷阴中导致下利。该方由黄芩、芍药、炙甘草和大枣(擘)四味中药组成,具有清热止痢、和中止痛之功,被誉为“治痢之祖方”[5]。清代医家王孟英[6]道:“黄芩汤苦寒直清里热,热伏于阴,苦味坚阴,乃正治也”,认为该方为治疗温病的主方。医家叶天士认为[7]:“黄芩汤以清为主,兼可化湿、理气等法,是治疗伏温实证之主方”。黄煌教授认为黄芩汤方中四味药有协同增效之功,临床应用是宜加不宜减[8]。在现代研究中,基于黄芩汤可以通过发挥其抑制肠道炎症协同化疗药物实现抗肿瘤的作用,耶鲁大学郑永齐教授及其团队运用标准化生产工艺,以黄芩汤原方为基础研发出抗肿瘤新药PHY906,后改名为YIV906[9]。临床上,黄芩汤以其特有的抗炎作用常常用于治疗溃疡性结肠炎、结肠癌、急性肠炎、腹泻、肝癌等疾病[10-13]。
现代研究发现,黄芩汤具有抑制炎症、调节肠道菌群以及抗氧化等作用,其抗炎功能在消化系统疾病中发挥主要作用[14-16]。当前对炎症通路的研究主要集中在Janus激酶/信号转导及转录激活因子(Janus Kinase/signal transducer and activator transcription,JAK/STAT)通路;丝裂原活化蛋白激酶(Mitogen-activated protein kinases,MAPK)通路;核因子-κB(Nuclear factor kappa B,NF-κB)信号通路3条经典通路 [17]。已有研究表明黄芩汤抗炎作用与其3条通路关系密切[18]。在细胞内活化后,3条通路会产生复杂的交汇的作用协同完成信号的传导,炎症因子肿瘤坏死因子-α(Tumor necrosis factorα,TNF-α)、白细胞介素-1(Interleukin 1,IL-1)、白细胞介素-6(Interleukin 6,IL-6)等信号传导就需要借助这3条信号通路。本课题组通过查阅国内外数据库近年来发表的关于黄芩汤应用于消化系统疾病的临床应用及实验研究的文献,对黄芩汤的抗炎作用以及在腹泻、溃疡性结肠炎、肝癌、胃癌等疾病的临床应用进行综述,旨在系统总结该方治疗消化系统疾病的临床应用及其抗炎的作用机制,从而为下一步进行深入研究提供思路。
腹泻是一种临床上常见的胃肠道疾病,中医将其归为“泄泻”的范畴,其临床症状往往表现为大便次数增多、便量增加以及粪质溏稀[19-20]。小儿腹泻往往是导致患儿营养不良、生长发育迟缓的重要诱因之一,急性小儿腹泻甚至危及患儿生命,约占全球儿童死亡的8.6%[21-22]。黄芩汤联合益生菌治疗腹泻可有效抑制IL-6、TNF-α、超敏C反应蛋白(Hypersensitive C-reactive protein,hs-CRP)在患者血清中的水平,有效改善患者腹痛、腹泻以及黏液脓血便的临床症状[23]。李孟等[24]研究发现运用黄芩汤治疗小儿湿热型腹泻时,采用随机对照试验发现该方较西药治疗效果显著且安全性高,其作用机制可能与黄芩汤能有效降低患儿血清中炎症因子IL-6、IL-10、TNF-α水平。腹泻往往与肠黏膜局部炎症关系密切[25],黄芩汤及其该方联用他法可有效降低患者血清中的炎症因子水平,调节机体免疫功能,改善患者腹痛泄泻等临床症状,缩短症状缓解时间,值得在临床上推广应用。
溃疡性结肠炎(Ulcerative colitis,UC)是一种特发性的以结肠黏膜慢性炎症为特征的疾病,临床表现常以腹痛、腹泻、里急后重和黏液脓血便为特征[26-27]。胡婕[28]发现黄芩汤加减联合美沙拉嗪疗法治疗UC可有效降低患者肠黏膜组织炎症因子TNF-α、IL-5和IL-6水平且提高患者血清中抑炎因子IL-10的水平,该方加减联合用药可有效抑制肠黏膜组织炎症因子分泌从而改善患者腹痛、腹泻以及血便等临床症状。朱卫芳等[29]观察黄芩汤颗粒剂联合美沙拉嗪治疗UC,对照组给予美沙拉嗪治疗,每组34人,治疗组总有效率97.05%高于对照组的82.35%,说明黄芩汤联合西药治疗UC疗效突出。王德芳等[13]选取134例湿热蕴结证UC患者,将接受口服柳氮磺吡啶治疗的患者设为对照组,试验组在其基础上运用黄芩汤加减联合针刺治疗进行疗效观察,结果发现黄芩汤加减联合他法可抑制患者血清中TNF-α、可溶性晚期糖基化终末产物受体(Soluble receptor for advanced glycation end products,s RAGE)分泌达到减轻肠黏膜炎症损伤,有效缓解患者临床症状提高患者生活质量。说明黄芩汤联合针刺或是西药对UC的治疗有效率高,值得在临床上推广。
结肠癌由胃肠道结肠或直肠内的上皮细胞发展而来的癌症,大部分患者采取手术后结合化疗的治疗方式,但仍有20%~30%的患者复发,该病往往不能治愈[30-31]。人体炎症环境对于该疾病的“炎-癌转化”有着极大影响[32]。宋振民等[33]将84例结肠癌患者随机分组,对照组采用环磷酰胺片联合静脉滴注甲氨蝶呤和5-氟尿嘧啶(Cyclophosphamide-Methotrexade-5-Fluorouracil,CMF)化疗方案,观察组采用口服加味黄芩汤联合CMF,结果显示治疗后运用黄芩汤加减联合CMF化疗方案的患者血清中干扰素-γ(IFN-γ)、IL-2水平高于对照组已经治疗前且血清中IL-4、IL-6水平明显降低,说明黄芩汤加减联合化疗治疗结肠癌可以抑制炎症反应,改善患者机体免疫力。除此之外,有学者研究发现黄芩汤联合足三里化脓灸可有效减轻结肠癌患者化疗后不良反应,增强患者免疫力,提高患者生活质量[34]。迟宏罡等[35]通过体外诱导人结肠癌SW620细胞的研究发现,黄芩汤可以有效抑制人结肠癌SW620细胞且黄芩汤的浓度越高对其的抑制率越强。以上说明,黄芩汤加味联合化疗对于结肠癌的治疗或者降低结肠癌患者化疗后不良反应疗效好且安全性高,值得在临床上推广。
原发性肝癌是临床中最常见的肿瘤疾病之一,2020年全球肿瘤疾病统计的数据显示全球肝癌的死亡率为8.3%[36-37]。李岩等[38]运用黄芩汤治疗原发性肝癌序贯肝动脉化疗栓塞术(Transcatheter arterial chemoembolization,TACE)术后患者进行疗效观察,结果显示术后给予黄芩汤治疗的患者总有效率更高,同时可以有效降低肝癌术后患者血清中NF-κB、HIF-1α含量,说明黄芩汤治疗原发性肝癌术后患者疗效好值得在临床中推广。王晓东等[39]选取120原发性肝癌患者随机分组治疗8周,对照组给予TACE,观察组在TACE的基础上加用黄芩汤,结果显示黄芩汤联合TACE与对照组相对更加有效可降低患者血清中NF-κB、HIF-1α、AFP水平从而发挥抗炎的效果。在TACE的基础上运用黄芩汤加减治疗原发性肝癌,治疗后患者血清中HIF-1α、VEGF、NF-κB均较治疗前减低且优于单一TACE治疗,且患者血清中谷草转氨酶(AST)、谷丙转氨酶(ALT)以及总胆红素(TBil)在治疗后指标明显降低,说明二者联合使用可减低炎症反应以及改善肝功能[40]。黄芩汤联合TACE治疗原发性肝癌可以有效降低患者血清中炎性因子水平从而达到更好的治疗效果。
胃癌是一种临床上常见的消化道恶性肿瘤,2020年全球肿瘤疾病统计的数据显示全球胃癌的死亡率是7.7%仅次于肝癌[36]。王金玲[41]运用黄芩汤治疗胃癌进行临床观察,采用随机法将208例胃癌患者进行分组,两组患者都进行化疗,观察组患者在此基础上口服黄芩汤,结果显示观察组患者血清中IL-6、IL-8、微血管密度(Microvessel density,MVD)水平明显低于对照组。张劭琴等[42]观察黄芩汤联合艾灸治疗化疗后胃癌患者疗效,结果显示黄芩汤联合艾灸有助于减少患者胃肠道不良反应,提高患者的生活质量,这可能与黄芩汤联合艾灸可以降低患者血清中炎症因子IL-6、IL-8水平有关。提示黄芩汤联合他法可降低患者血清中炎症因子指标,同时对改善胃癌患者化疗后不良反应及提高患者生活治疗方面发挥着巨大的积极作用。
研究发现,黄芩汤可以通过多靶点多信号通路抑制血清中的炎症因子水平以发挥其抗炎的药理作用。黄芩汤全方成分较为复杂,研究发现该方主要成分有黄芩素、汉黄芩素、黄芩苷、汉黄芩苷、芍药苷、甘草酸等[43-45]。刘雅清等[18]通过脂多糖(Lipopolysaccharide,LPS)诱导RAW264.7细胞活化创建细胞炎症模型,研究发现炎症细胞经过黄芩汤作用后可以有效抑制细胞内p38 MAPK总蛋白、NF-κB p65总蛋白、JAK总蛋白表达以及JAK m RNA的表达,达到减弱炎性因子产生与释放的目的,发挥黄芩汤的抗炎作用。黄钰芳等[46]优化黄芩提取工艺进行体外抗炎实验,结果显示在黄芩提取物终浓度为50~350 mg·mL-1时,黄芩提取物可以显著抑制RAW264.7炎性细胞模型NO的释放发挥其抗炎活性。周羽[47]研究发现将黄芩苷与芍药苷协同应用,其实现抗炎的最佳浓度是5μg/mL,两者联合使用能有效降低NF-κB p65和IκBα磷酸化的表达,抑制NF-κB的表达。
JAK/STAT信号通路被认为是细胞功能的中心通信节点之一,参与了细胞增殖、分化、凋亡、免疫调节等重要过程,当前该通路的研究与炎症疾病及肿瘤疾病关系密切[48-49]。纪佳等[50]观察黄芩汤治疗UC大鼠对IL-6/JAK/STAT3信号通路的影响,运用2,4,6-三硝基苯磺酸(TNBS)建立大鼠UC模型,经黄芩汤干预后,大鼠结肠黏膜明显恢复且炎症细胞明显减少,大鼠体内IL-6 mRNA、JAK mRNA、STAT3 mRNA显著减少,表明黄芩汤可以通过IL-6/JAK/STAT3信号通路调节肠道功能,抑制炎症反应。此外,有学者研究发现黄芩汤可以通过IFN-γ/JAK/ETS信号通路实现减少大鼠UC模型的肠道炎症和细胞凋亡从而达到改善UC的目的,经黄芩汤干预后可显著下调IFN-γ、JAK2的蛋白表达以及ETS的表达,提示黄芩汤经调控IFN-γ/JAK/ETS信号通路改善UC[51]。HUANG J B等[52]通过运用葡聚糖硫酸钠(Dextran sodium sulfate,DSS)联合氧化偶氮甲烷(Azoxymethane,AOM)诱导的结肠癌小鼠模型,研究发现在黄芩汤基础上加味藤梨根可以更加显著地降低小鼠结肠组织中IL-6 mRNA、IL-17 mRNA以及STAT3蛋白的水平,说明黄芩汤加藤梨根可以通过调节IL-6/STAT3信号通路实现对结肠癌的干预。王倩等[53]通过三硝基苯磺酸(Trinitro-Benzenesulfonicacid,TNBS)诱导的结肠炎大鼠模型,运用加味黄芩汤干预后可以降低大鼠结肠组织中IL-6mRNA、STAT3的表达,且还可以降低大鼠血清中炎症因子IL-6、TNF-α、PGE2的含量,表明黄芩汤加味可调节信号通路IL-6/STAT3达到缓解结肠组织炎症的目的。以上结果提示,黄芩汤可以通过调控JAK/STAT相关通路实现抑制炎症的作用。
MAPK主要有细胞外信号调节激酶(ERK MAPK)、c-Jun氨基末端激酶(c-Jun N-terminal kinase,JNK)和p38MAPK 3个亚族[54],他们与MAPK组成3条最具代表性的通路,这些通路的激活可加快细胞凋亡刺激炎症反应[55]。有研究表明[18],由LPS诱导构建RAW264.7炎症细胞模型,经黄芩汤干预后细胞内p38 MAPK总蛋白、ERK总蛋白、JNK总蛋白均随着黄芩汤浓度的增加而降低,且细胞上清液中IL-6、TNF-α、PGE2炎症因子也明显下降,说明黄芩汤可以限制MAPK信号通路的激活抑制减低炎症因子的产生以实现其抗炎的作用。PU W L等[56]通过青霉素研究发现黄芩素可以通过抑制MAPK信号通路,减轻了青霉素诱导小鼠胰腺炎,降低炎症介质的分泌水平,显著抑制胰腺的炎症反应。段雲霄[57]通过上调miR-7表达联合黄芩素干预胃癌细胞SGC-7901,在48 h后与未经黄芩素干预的细胞组相比,经黄芩素干预的细胞的MAPK p38和MAPK/ERK的蛋白表达显著下降,高表达miR-7和联合黄芩素干预可通过调控MAPK/ERK信号通路达到抑制胃癌细胞的作用。以上结果提示,黄芩汤及其该方主要成分可以通过调控MAPK相关信号通路达到抑制炎症的作用。
NF-κB是一种普遍存在的转录因子,可调节多种炎症和免疫基因的表达以实现机体防御和抗炎的作用[58]。YAN B F等[14]采用高脂饮食建立非酒精性脂肪肝病(Non-alcoholic fatty liver disease,NAFLD)大鼠模型,利用免疫组化分析得出大鼠血清中TNF-α、IL-6和IL-1β水平升高证明肝脏中存在强烈的炎症反应,运用免疫印迹法(Western blotting,WB)检测出黄芩汤组大鼠的肝脏中TLR4、NF-κB、p-NF-κB及其下游NLRP3炎症相关蛋白的蛋白水平,结果显示黄芩汤可以有效降低其蛋白水平,说明黄芩汤可以经TLR4/NF-κB/NLRP3通路有效缓解了NAFLD大鼠模型的肝脏炎症。左玲等[59]通过高脂高糖联合三硝基苯磺酸建立湿热型UC大鼠模型,对照组给予柳氮磺吡啶混悬液,观察组采用黄芩汤灌胃两周,结果显示黄芩汤可以限制NFκB的激活,进而降低ICAM-1表达,从而实现了抑制炎症反应,促进溃疡修复,调节肠道功能。王康等[60]采用3%葡聚糖硫酸钠水溶液构造UC小鼠动物模型,给予动物模型高、中、低3种不同剂量的加味黄芩汤,结果发现加味黄芩汤高剂量组效果最优,可以有效抑制炎症细胞分泌、缓解结肠组织水肿和黏膜表面糜烂,其作用机制加味黄芩汤可以影响STAT3/NFκB/IL-6通路从而降低结肠组织中STAT3、NF-κB、IL-6mRNA及蛋白表达水平。从以上结果表明,黄芩汤可通过调控NF-κB相关通路来实现抑制炎症的作用。
炎症是机体对感染和组织损伤的一种保护性反应[61],巨噬细胞在炎症反应过程中发挥着关键作用,根据组织微环境和激活途径可将巨噬细胞可分为M1型巨噬细胞(Classically activated macrophage)和M2型巨噬细胞(Alternatively activated macrophage)两种亚型[62-64]。LI M Y等[65]研究发现黄芩汤显著降低M1型巨噬细胞主要标志物iNOS和CXCL10的表达且参与M1型巨噬细胞极化的促炎细胞因子IL-1b和IL-6水平明显减低,抑制了RasPI3KAKT-HIF-1a和NF-κB通路从而实现减轻炎症反应。LI M Y等[66]通过运用黄芩汤对DSS诱导的UC小鼠灌胃治疗发现,黄芩汤可以通过激活通路FFAR4-AMPK-PPARα且促进巨噬细胞M1型向M2型极化与抗炎因子结合达到抗炎的目的。CHANGOU C A等[67]研究发现HIY-906可通过增强干扰素γ从而使M1巨噬细胞极化且抑制IL-4以达到抗感染和抗肿瘤的目的。提示黄芩汤可以通过调控巨噬细胞极化抑制炎症因子分泌的水平实现良好的抗炎效果。
黄芩汤在临床应用中多取其清热止痢之效,治疗各种湿热下利的疾病,因具有较好的抗炎作用,将其用于多种疾病的炎性阶段并得到了良好的临床效果。现代医学研究发现黄芩汤具有抗炎的药理作用以及人体炎症环境对疾病“炎癌转化”过程的影响,通过其抗炎抗感染的作用,将该方运用于消化系统疾病中伴随炎症反应的感染性疾病以及肿瘤疾病。临床上黄芩汤及其该方联合他法多用于治疗腹泻、溃疡性结肠炎、结肠癌、原发性肝癌、胃癌等疾病,能明显改善患者腹痛、腹泻以及脓血便等临床症状。研究发现黄芩汤可以通过调控JAK/STAT相关信号通路、MAPK相关信号通路和NF-κB相关信号通路实现抑制炎症因子分泌达到抗炎的作用,还可以调控巨噬细胞的极化以实现降低血清中炎症因子水平。因此,我们可以得出黄芩汤发挥抗炎作用的机制是多通路共同调控的结果且这些通路之间存在相互影响,然而目前未见相关文献报道。
尽管黄芩汤在抗炎作用方面已有相关研究,但是仍有一些问题尚未解决:(1)关于黄芩汤的抗炎作用机制有待完善,限制了黄芩汤的临床使用范围,可结合临床进一步研究;(2)对于黄芩汤应用于其他系统疾病的临床试验和基础实验鲜见报道,可以扩大研究范围;(3)对黄芩汤的理论性探讨报道相对较少,有必要重视理论研究、临床研究和实验研究三者之间的关系。本文系统性地总结黄芩汤在消化系统疾病中的临床应用及其抗炎作用,以期为扩大该方的临床应用范围提供支撑依据,也为该方的进一步研究提供思路。
  • 国家自然科学基金面上项目(82274496)
  • 河南省科技研发计划联合基金项目(222301420021)
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2025年第43卷第5期
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doi: 10.13193/j.issn.1673-7717.2025.05.027
  • 首发时间:2026-10-30
  • 出版时间:2025-05-10
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国家自然科学基金面上项目(82274496)
河南省科技研发计划联合基金项目(222301420021)
作者信息
    1.河南中医药大学中医学院,河南 郑州 450046
    2.河南省豫药全产业链研发河南省协同创新中心,河南 郑州 450046
    3.河南中医药大学中医药科学院,河南 郑州 450046
    4.河南省中医院,河南中医药大学第二附属医院,河南 郑州 450046

通讯作者:

张楠(1989-),女,河南南阳人,副教授,博士,研究方向:方剂配伍及作用机理规律。E-mali:。
许二平(1962-),男,河南鄢陵人,教授,博士研究生导师,博士,研究方向:方剂配伍及作用机理规律。E-mail:。
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https://castjournals.cast.org.cn/joweb/zhzyyxk/CN/10.13193/j.issn.1673-7717.2025.05.027
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2种不同金属材料的力学参数
科
Family
属数
Number of
genus
种数
Number of
species
占总种数比例
Percentage of
total species (%)
属
Genus
种数
Number of
species
占总种数比例
Percentage of total
species (%)
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
栓菌属 Trametes 5 2.39
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