Article(id=1322926042083635200, tenantId=1146029695717560320, journalId=1255847919539208197, issueId=1322925862630339452, articleNumber=null, orderNo=null, doi=10.13193/j.issn.1673-7717.2025.07.013, 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=1793339747210, onlineDateStr=2026-10-30, pubDate=1752076800000, pubDateStr=2025-07-10, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1793339747210, onlineIssueDateStr=2026-10-30, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1793339747210, creator=13701087609, updateTime=1793339747210, updator=13701087609, issue=Issue{id=1322925862630339452, tenantId=1146029695717560320, journalId=1255847919539208197, year='2025', volume='43', issue='7', pageStart='1', pageEnd='258', issueExtLink='null', onlineDate='null', pubDate='1752076800000', pubDateStr='2025-07-10', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=0, createTime=1793339704424, creator='13701087609', updateTime=1793340532184, updator='13701087609', preIssue=null, nextIssue=null, articleTotal=null, ext={EN=IssueExt(id=1322929334587105328, tenantId=1146029695717560320, journalId=1255847919539208197, issueId=1322925862630339452, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1322929334587105329, tenantId=1146029695717560320, journalId=1255847919539208197, issueId=1322925862630339452, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null, downloadFileDto=null}, startPage=58, endPage=62, ext={EN=ArticleExt(id=1322926042301739009, articleId=1322926042083635200, tenantId=1146029695717560320, journalId=1255847919539208197, language=EN, title=Exploring Formation and Intervention of Breast Cancer Based on Theory of “Depression and Toxin Leading to Deficiency”, columnId=1256183361521967297, journalTitle=Chinese Archives of Traditional Chinese Medicine, columnName=Target on National Project, runingTitle=null, highlight=null, articleAbstract=

The theory of“depression and toxin leading to deficiency”holds that the pathological products such as dampness,phlegm,heat and blood stasis caused by excessive anger and depression,Qi stagnation,impaired Zang-Fu function,imbalance of internal environment of the body and metabolic disorder of Qi,blood and body fluid are the initiating factors of carcinogenesis. The key pathogenesis of the occurrence and development of breast cancer is“depression-toxin intertwining,spread of cancer toxin,deficiency caused by cancer,and mutual injury of deficiency and toxin”.“Multi-cause intersection and transformation of cancer toxin”is the core driver of breast cancer. Under the background of modern medicine,“heat toxin injuring Yin essence”,“toxin impairing Qi and blood”and“deficiency fire stagnating heat”are the main pathogenesis evolution of breast cancer radiotherapy,chemotherapy and endocrine therapy,respectively.“Driving away pathological factors and leaving body deficiency”and“residual toxin flowing”are closely related to breast cancer surgery and recurrence and metastasis,respectively. Professor LIU Caigang,in view of the complex pathogenesis of“depression and toxin leading to deficiency”of breast cancer and the complications after modern medical intervention,adopted the modern research and development checkpoint therapeutic target database(CKTTD),combined with the theory of traditional Chinese medicine,explored the advantages of anti-cancer traditional Chinese medicine,and carried out the research of traditional Chinese and Western medicine around cancer-related fatigue,chemotherapy resistance,macroscopically adjusting the body's healthy Qi deficiency and depression and microscopically treating the target of cancer toxins. Several medical institutions represented by Shenbailing Granules(参百灵颗粒)have been developed,and a series of large-sample,multi-center,randomized controlled studies have been carried out to form an“efficient,low-toxic,individualized”breast cancer diagnosis and treatment strategy.

, authors=Xiaoyu GAO1, 2, 3, Nan NIU1, 2, Dongxiao ZHANG4, Yunhai GAO5, Fei YU1, Suning CHEN1, Wenping WANG3, Ling HAN2, 6, Liang WANG2, 6, Jinhong LENG2, 5, Caigang LIU1, 2, authorsList=Xiaoyu GAO, Nan NIU, Dongxiao ZHANG, Yunhai GAO, Fei YU, Suning CHEN, Wenping WANG, Ling HAN, Liang WANG, Jinhong LENG, Caigang LIU, authorCompany=null, correspAuthors=Caigang LIU, 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=1322926042687614978, articleId=1322926042083635200, tenantId=1146029695717560320, journalId=1255847919539208197, language=CN, title=基于“郁毒致虚”理论探讨乳腺癌的形成与干预, columnId=1256183362172142382, journalTitle=中华中医药学刊, columnName=国家项目点击, runingTitle=null, highlight=null, articleAbstract=

“郁毒致虚”理论认为,忧怒抑郁过激,气郁始成,脏腑功能受损,机体内环境失衡,气血津液代谢障碍产生的湿、痰、热、瘀等病理产物是癌变的始动因素。“郁毒搏结、癌毒蔓生、因癌致虚、虚毒互伤”是乳腺癌发生发展的关键病机,“多因交合、癌毒转化”是乳腺癌发生的核心驱动程序。现代医学背景下“热毒伤阴”“毒损气血”“虚火郁热”分别是乳腺癌放疗、化疗和内分泌治疗的主要病机演变,“实去虚存”与“余毒流注”分别与乳腺癌手术及复发转移密切相关。刘彩刚教授针对乳腺癌“郁毒致虚”的复合病机及现代医学干预后出现的并发症,采用团队自主研发的中药现代化研发工具-肿瘤免疫知识图谱CKTTD,结合传统中医学理论,挖掘抗肿瘤优势中药组方,围绕癌因性疲乏、化疗耐药等病症开展中西医联合攻关,从宏观调正虚之态、纠郁毒之偏,从微观打癌毒之靶。现已研发出以参百灵颗粒为代表的多个医疗机构制剂,并通过开展一系列大样本、多中心、随机对照研究,形成“高效、低毒、个体化”的乳腺癌诊疗策略。

, authors=高晓宇1, 2, 3, 牛楠1, 2, 张董晓4, 高允海5, 于飞1, 陈苏宁1, 王文萍3, 韩凌2, 6, 王亮2, 6, 冷锦红2, 5, 刘彩刚1, 2, authorsList=高晓宇, 牛楠, 张董晓, 高允海, 于飞, 陈苏宁, 王文萍, 韩凌, 王亮, 冷锦红, 刘彩刚, authorCompany=null, correspAuthors=刘彩刚, authorNote=

高晓宇(1989-),女,吉林长春人,副主任医师,硕士研究生导师,博士,研究方向:中西医结合防治肿瘤及心脑血管疾病。

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刘彩刚(1981-),男,山东潍坊人,教授,博士研究生导师,博士,研究方向:中西医结合防治肿瘤。E-mail:。
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高晓宇(1989-),女,吉林长春人,副主任医师,硕士研究生导师,博士,研究方向:中西医结合防治肿瘤及心脑血管疾病。

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高晓宇(1989-),女,吉林长春人,副主任医师,硕士研究生导师,博士,研究方向:中西医结合防治肿瘤及心脑血管疾病。

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基于“郁毒致虚”理论探讨乳腺癌的形成与干预
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高晓宇 1, 2, 3 , 牛楠 1, 2 , 张董晓 4 , 高允海 5 , 于飞 1 , 陈苏宁 1 , 王文萍 3 , 韩凌 2, 6 , 王亮 2, 6 , 冷锦红 2, 5 , 刘彩刚 1, 2
中华中医药学刊 | 国家项目点击 2025,43(7): 58-62
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中华中医药学刊 |国家项目点击 2025 , 43 (7) : 58 -62
基于“郁毒致虚”理论探讨乳腺癌的形成与干预
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高晓宇(1989-),女,吉林长春人,副主任医师,硕士研究生导师,博士,研究方向:中西医结合防治肿瘤及心脑血管疾病。

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高晓宇(1989-),女,吉林长春人,副主任医师,硕士研究生导师,博士,研究方向:中西医结合防治肿瘤及心脑血管疾病。

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高晓宇1, 2, 3, 牛楠1, 2, 张董晓4, 高允海5, 于飞1, 陈苏宁1, 王文萍3, 韩凌2, 6, 王亮2, 6, 冷锦红2, 5, 刘彩刚1, 2
作者信息
  • 1.中国医科大学附属盛京医院,辽宁 沈阳 110004
  • 2.辽宁省肿瘤中医药多学科交叉创新团队,辽宁 沈阳 110004
  • 3.辽宁中医药大学,辽宁 沈阳 110847
  • 4.首都医科大学附属北京中医医院,北京 100010
  • 5.辽宁中医药大学附属医院,辽宁 沈阳 110032
  • 6.华润三九医药股份有限公司,广东 深圳 518110
通讯作者:
刘彩刚(1981-),男,山东潍坊人,教授,博士研究生导师,博士,研究方向:中西医结合防治肿瘤。E-mail:。
作者简介:

高晓宇(1989-),女,吉林长春人,副主任医师,硕士研究生导师,博士,研究方向:中西医结合防治肿瘤及心脑血管疾病。

Exploring Formation and Intervention of Breast Cancer Based on Theory of “Depression and Toxin Leading to Deficiency”
Xiaoyu GAO1, 2, 3, Nan NIU1, 2, Dongxiao ZHANG4, Yunhai GAO5, Fei YU1, Suning CHEN1, Wenping WANG3, Ling HAN2, 6, Liang WANG2, 6, Jinhong LENG2, 5, Caigang LIU1, 2
Affiliations
  • 1.Shengjing Hospital of China Medical University,Shenyang 110004,Liaoning,China
  • 2.Liaoning Provincial Tumor Chinese Medicine Multidisciplinary Interdisciplinary Innovation Team,Shenyang 110004,Liaoning,China
  • 3.Liaoning University of Traditional Chinese Medicine,Shenyang 110847,Liaoning,China
  • 4.Beijing Hospital of Traditional Chinese Medicine,Beijing 100010,China
  • 5.Affiliated Hospital of Liaoning University of Traditional Chinese Medicine,Shenyang 110032,Liaoning,China
  • 6.China Resources Sanjiu Pharmaceutical Co.,Ltd,Shenzhen 518110,Guangdong,China
出版时间: 2025-07-10 doi: 10.13193/j.issn.1673-7717.2025.07.013
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“郁毒致虚”理论认为,忧怒抑郁过激,气郁始成,脏腑功能受损,机体内环境失衡,气血津液代谢障碍产生的湿、痰、热、瘀等病理产物是癌变的始动因素。“郁毒搏结、癌毒蔓生、因癌致虚、虚毒互伤”是乳腺癌发生发展的关键病机,“多因交合、癌毒转化”是乳腺癌发生的核心驱动程序。现代医学背景下“热毒伤阴”“毒损气血”“虚火郁热”分别是乳腺癌放疗、化疗和内分泌治疗的主要病机演变,“实去虚存”与“余毒流注”分别与乳腺癌手术及复发转移密切相关。刘彩刚教授针对乳腺癌“郁毒致虚”的复合病机及现代医学干预后出现的并发症,采用团队自主研发的中药现代化研发工具-肿瘤免疫知识图谱CKTTD,结合传统中医学理论,挖掘抗肿瘤优势中药组方,围绕癌因性疲乏、化疗耐药等病症开展中西医联合攻关,从宏观调正虚之态、纠郁毒之偏,从微观打癌毒之靶。现已研发出以参百灵颗粒为代表的多个医疗机构制剂,并通过开展一系列大样本、多中心、随机对照研究,形成“高效、低毒、个体化”的乳腺癌诊疗策略。

乳腺癌  /  郁毒致虚  /  中医病机  /  治则治法

The theory of“depression and toxin leading to deficiency”holds that the pathological products such as dampness,phlegm,heat and blood stasis caused by excessive anger and depression,Qi stagnation,impaired Zang-Fu function,imbalance of internal environment of the body and metabolic disorder of Qi,blood and body fluid are the initiating factors of carcinogenesis. The key pathogenesis of the occurrence and development of breast cancer is“depression-toxin intertwining,spread of cancer toxin,deficiency caused by cancer,and mutual injury of deficiency and toxin”.“Multi-cause intersection and transformation of cancer toxin”is the core driver of breast cancer. Under the background of modern medicine,“heat toxin injuring Yin essence”,“toxin impairing Qi and blood”and“deficiency fire stagnating heat”are the main pathogenesis evolution of breast cancer radiotherapy,chemotherapy and endocrine therapy,respectively.“Driving away pathological factors and leaving body deficiency”and“residual toxin flowing”are closely related to breast cancer surgery and recurrence and metastasis,respectively. Professor LIU Caigang,in view of the complex pathogenesis of“depression and toxin leading to deficiency”of breast cancer and the complications after modern medical intervention,adopted the modern research and development checkpoint therapeutic target database(CKTTD),combined with the theory of traditional Chinese medicine,explored the advantages of anti-cancer traditional Chinese medicine,and carried out the research of traditional Chinese and Western medicine around cancer-related fatigue,chemotherapy resistance,macroscopically adjusting the body's healthy Qi deficiency and depression and microscopically treating the target of cancer toxins. Several medical institutions represented by Shenbailing Granules(参百灵颗粒)have been developed,and a series of large-sample,multi-center,randomized controlled studies have been carried out to form an“efficient,low-toxic,individualized”breast cancer diagnosis and treatment strategy.

breast cancer  /  depression and toxin leading to deficiency  /  pathogenesis of traditional Chinese medicine  /  therapeutic principle and method
高晓宇, 牛楠, 张董晓, 高允海, 于飞, 陈苏宁, 王文萍, 韩凌, 王亮, 冷锦红, 刘彩刚. 基于“郁毒致虚”理论探讨乳腺癌的形成与干预. 中华中医药学刊, 2025 , 43 (7) : 58 -62 . DOI: 10.13193/j.issn.1673-7717.2025.07.013
Xiaoyu GAO, Nan NIU, Dongxiao ZHANG, Yunhai GAO, Fei YU, Suning CHEN, Wenping WANG, Ling HAN, Liang WANG, Jinhong LENG, Caigang LIU. Exploring Formation and Intervention of Breast Cancer Based on Theory of “Depression and Toxin Leading to Deficiency”[J]. Chinese Archives of Traditional Chinese Medicine, 2025 , 43 (7) : 58 -62 . DOI: 10.13193/j.issn.1673-7717.2025.07.013
乳腺癌属于中医“乳岩”,归属“积聚”“癥瘕”范畴。由于人口基数大,我国乳腺癌的发病和死亡绝对数量均位列全球首位。随着现代医学的发展和新型药物的不断出现,西医治疗乳腺癌取得了不错的效果。但患者在治疗前、治疗中、治疗后及康复阶段出现的诸如疲乏、失眠、抑郁、焦虑情绪,西医无法完全兼顾;治疗引起的不良反应,如化疗耐药、恶心呕吐、骨髓抑制、周围神经损伤、放射性肺损伤、内分泌中相关骨关节症状等问题,西医缺乏相对成熟的治疗方案;对于终末期乳腺癌患者,西医更是鞭长莫及。针对西医的难点和盲区,中西医结合在乳腺癌上述病症的综合治疗方面占有一定的地位。2022年国务院办公厅印发的《“十四五”国民健康规划》及《关于印发“十四五”中医药发展规划的通知》中强调要彰显中医药在肿瘤诊治的特色优势,做优做强包括肿瘤在内的中医优势专科专病;2023中国整合肿瘤学大会(Chinses congress on holistic integrative oncology,CCHIO)提出“肿瘤防治、赢在整合”,倡导中西医并重。肿瘤是全身系统性疾病,手术治疗尚不能一劳永逸,乳腺癌急需开展中西医联合攻关,进行全周期、多阶段的管理。
刘彩刚教授,主任医师,博士研究生导师,教育部长江学者特聘教授,国家百千万人才工程有突出贡献中青年专家,师承第四批国医大师、首批全国名中医张静生教授,是全国西学中优秀人才,长期致力于抗肿瘤中药新药研发与中西医结合肿瘤诊治。国医大师张静生提倡临床科研并重,衷中参西,是辽宁省中西医结合事业的开拓者[1]。在张老的影响下,刘彩刚教授提倡现代医学和中医互为君臣,精准医学为佐,医学人文为使调剂各方,创新性提出乳腺癌“郁毒致虚”理论。刘彩刚教授认为乳腺癌的形成是一个复杂的过程,人体正气的强弱、致病邪气的性质是乳腺癌发生、发展及变化之本。忧怒抑郁过激,气郁始成,导致脏腑功能受损,机体内环境失衡,气血津液代谢障碍产生的湿、痰、热、瘀等病理产物是癌变的始动因素;“郁毒搏结、癌毒蔓生、因癌致虚、虚毒互伤”是乳腺癌发生发展的关键病机,“多因交合、癌毒转化”是乳腺癌发生的核心驱动程序。现将“郁毒致虚”病机理论辨治乳腺癌探讨如下。
喜、怒、忧、思、悲、恐、惊七种情志活动过激,超出人体正常的承受范围即成为致病因素。朱丹溪在《格致余论》曰:“忧怒抑郁,朝夕积累,脾气消阻,肝气积逆,遂成隐核,……名曰乳岩。”《外科正宗》言:“忧郁伤肝,思虑伤脾,积想在心,所愿不得志者,致经络痞涩,聚结成核……名曰乳岩”。《外科问答》亦曰:“翻花岩,……由肝郁不舒,水火鸱张而得,甚不易治。”均强调了乳腺癌的发生与七情郁滞密切相关。国医大师周仲瑛认为乳腺癌起于无形之气,总以气郁为先[2],提示乳癌的防治首先要从调畅情志、解除七情搏结入手。
肝喜条达恶抑郁,长期情志不畅,肝失条达,疏泄失常,气机不畅,津液代谢失常,痰湿之邪产生。同时,肝失疏泄,横逆犯脾,脾土受伐,运化失职,水谷不化,痰湿内蕴加重。气有余便是火,气郁日久化火,炼津成痰,煎血成瘀,痰瘀互结,日久易酿湿热、热毒之邪。总而言之,七情郁滞导致多脏腑功能失司,气、血、津、液代谢异常,出现湿、痰、热、瘀等病理产物,气滞血瘀痰浊等聚生癌毒是癌变的始动因素,上行阻于乳络,积于乳房,结块丛生,发为乳岩。
毒邪学说是中医学的经典理论之一。《素问·五常政大论篇》曰:“夫毒者,皆五行标盛暴烈之气所为也”,在正气亏虚的基础上,邪之甚者或蕴结日久即可成毒[3],诸多疑难重症均与毒邪相关。毒邪有内毒与外毒之别:内毒多因情志内伤及病理产物蕴结日久而成,前文所说郁证所致的气血津液代谢障碍、脏腑功能失调所产生的病理产物即是毒邪之一;外毒则多指感染六淫邪气、疫戾之气或有毒致癌物蕴聚演化而成。
“外感伏毒”是乳腺癌发生的重要因素。《灵枢·九针论》中的“四时八风之客于经络之中,为瘤病者也”,提出瘤病的发生与外感六淫有关。对于乳腺癌,当肝胃经不畅,外感六淫之邪可导致气血运行不畅,痰浊瘀血内停,阻塞经脉,积久成毒,伏而发病,变生乳岩。除外传统外感六淫,现代生活中放射线尤其是青春期的电离辐射暴露,罹患乳腺癌的风险极高;其次,苯并芘是人类致癌物,它广泛存在于烟草、内燃机尾气、烟雾及烹饪油烟等介质中,长期接触可提高乳腺癌致病率及女性后代患乳腺癌的风险[4];此外,长期从事油染、化工、理发、化工溶剂等工作的女性发生乳腺癌的危险性增加。电离辐射、苯并芘、漆毒等均属外邪侵袭,邪入胞中冲任损伤,日久伏而发病,使得“外感伏毒”的范围进一步拓展。
此外,饮食内伤、劳逸失宜及特殊药物摄入均是乳腺癌发病的因素。乙醇会导致女性体内雌激素水平升高,经常饮酒增加乳腺癌患病风险。生殖因素、口服避孕药、肥胖、摄入高脂肪高热量食物均是乳腺癌易感因素[5]。除外上述非遗传因素,在同等暴露环境下,个体之间的发病风险仍存在差异,提示遗传背景同样影响了乳腺癌的易感性[6-7],尤其是携带BRCA1/2等易感基因的女性,其“胞胎传毒”极大地影响着疾病的发生。
综上,七情郁滞、外感伏毒、胞胎传毒与乳腺癌发生关系最为密切。多因交合,郁毒搏结,量变引发质变,最终形成癌毒转化。
国医大师周仲瑛提出癌毒理论[8],“癌毒”是肿瘤的特异性致病因子,其区别于湿、痰、热、瘀等病理产物,但它们之间又存在密不可分的内在联系。历代文献中也多有以“毒”论乳腺癌的记载,如宋代杨士瀛在《仁斋直指方·卷二十二发癌方论》中指出:“癌者,上高下深,岩穴之状,……毒根深藏,穿孔透里,……妇则多发于乳”。其间“毒根深藏”“穿孔透里”是乳腺癌癌毒之邪具有隐匿性、顽固性、流窜性、穿透性的形象体现,这与现代医学所论的乳腺癌病理有异曲同工之妙。《金匮要略心典》中言:“毒,邪气蕴结不解之谓”。毒可视作诸多病邪的进一步发展,日久不去,多化生成毒,如七情过极化火生毒、痰浊阻滞日久而成痰毒、瘀血停蓄日久而成瘀毒等,正如国医大师周仲瑛所说“毒必附邪,邪盛生毒,毒因邪而异性,邪因毒而鸱张,以痰瘀为依附而成形,耗精血自养而增生”。
可见,癌毒属毒邪之一,是在“郁毒搏结”长期刺激下诱导产生的一类特异性致病因子,此为“病因之毒”。同时癌毒作为机体偏颇的一种状态,也是“病理产物之毒”,一旦蕴育而成贯穿肿瘤始终,与肿瘤的增殖、侵袭、转移等恶性行为密切相关。“癌毒”具有隐匿性、猛烈性、流窜性、顽固性和损正性[9]。乳腺癌“癌毒蔓生”病机繁杂,多以痰毒、瘀毒、热毒为患,临床辨治应“审证求机”,以不同毒邪的特点进行辨证论治、方可取得良效。
(1)痰毒:国医大师张学文认为乳腺癌的主要病机为正气不足,痰气交结[10]。肝失疏泄,脾失健运,肾失气化,则津凝液聚为痰,加之郁毒壅塞经络,搏结成“痰毒”,留注乳络,形成肿块,或软或硬,或坚硬如岩,推之不移。
(2)瘀毒:气郁在先,肝气不畅,郁毒瘀滞,气滞则血行瘀滞;肝郁化火,耗伤阴液,阴血凝聚则成瘀;肾气不足则血运无力,肾阳虚衰则血失温煦,肾阴亏虚则灼阴血伤,皆可出现血瘀。瘀血凝滞,与毒邪搏结,“瘀毒”内阻于乳络发为肿块。
(3)热毒:情志不畅、郁怒不舒,郁毒日久化热生火;或感染火热之邪入血分,酿成热毒;或痰瘀胶结日久,郁而化热,均可形成“热毒”。热毒与“炎-癌转化”机制类似[11],血热搏结,运行失常,热毒壅阻乳络,日久成积,发为癌瘤。热毒壅盛蕴结乳中,日久可见皮肉紫黑,瘤核坚硬,甚则溃烂渗流臭污血水。
综上乳腺癌“癌毒蔓生”病机繁杂,多以痰毒壅塞、瘀毒凝滞、热毒郁积,炼液成块。病位在乳房,与肝肾关系密切,涉及脾、胃、冲任二脉,癌毒与痰瘀等相互胶结形成了乳腺癌的复合病机[12-13],是从无形之邪到有形实邪的过程。
内生之癌毒其性暴戾,伏毒锢结,难解难散,耗伤正气;现代医学治疗手段加重机体气血阴阳偏颇,最终“因癌致虚”,形成“虚毒互伤”之态,具体病因病机如下。
首先,《素问·刺法论篇》中道:“正气存内,邪不可干。邪之所凑,其气必虚”;明代李中梓《医宗必读》曰:“积之成也,正气不足,而后邪气踞之”,强调正气不足与肿瘤的发生有关。乳腺癌的发病率在45~65岁维持较高水平,这与中年之后机体组织器官衰退、免疫力低下有关,正气亏虚相关。其次,肿瘤作为的病理产物,癌毒肆虐,狂夺精微以自养,瘤体不断长大,大量耗伤人体精、气、血、津液,正气日益虚损,气血津液郁滞愈深,癌毒日益炽盛,长此以往,恶性循环[14];同时癌毒之邪胜正气而失于约束,四处转移扩散,毒邪随经络、血脉流注到五脏六腑,导致脾胃虚弱,气血无以化生,这两点均可导致“因癌致虚”。第三,化疗毒损气血、放疗耗伤气阴,现代医学治疗手段在改善病灶的同时对机体产生新的“毒邪”,导致“因毒致虚”。最后,乳腺癌手术会损伤人体正气及气血,手术创伤可造成急性虚证,属于“因创致虚”。综上,正气亏虚、因癌致虚、因毒致虚、因创致虚,最终导致“虚毒互伤”之态。基于乳腺癌“因癌致虚、虚毒互伤”病机演变规律,“扶正祛邪、抗癌解毒”是治疗乳腺癌的基本原则。
放疗通过放射性粒子束杀伤恶性肿瘤细胞,放射性粒子束属于高能量聚合,对细胞的杀伤属性类似火热毒邪对机体的破坏[15],《素问·阴阳应象大论篇》中云:“热伤气”,放疗热毒耗气伤阴,热灼络脉,气虚血脉涩滞,热盛肉腐。伤于肺络,肺热叶焦,则干咳、胸闷胸痛、痰中带血,发为放射性肺炎(radiation pneumonitis,RP)。RP现代医学治疗以激素、抗生素为主,目前尚无RP的诊疗规范及特效治疗手段。按照中医理论,“毒”为药物的总称,凡药物皆有毒,《黄帝内经》根据性质,将其分为大毒、常毒、小毒和无毒四类。中医学者根据放疗后患者的临床表现,将放疗归属于“大毒”范畴,其毒具有“火热毒邪,灼津耗气”的特性。放射性肺炎的病机关键在于“热毒伤阴”,放疗热毒弥漫,损及气阴,灼伤膜络,虽有疲乏征象,也需谨慎温补,防止放疗热毒炽燃,可采用活血清热解毒类中药配合养阴生津、补益固本类中药分期论治。同时,放射性肺炎的治疗应做到未病先防,放疗的设计和审核是关键,当毒性过大时,可采用病灶部分照射的方法,做到“大毒治病,十去其六”[16]。刘彩刚教授团队采用医工结合研发的束波刀E10,以高能聚焦超声机械效应为主、结合超声实时精准定位和AI智能分析治疗方案,具有低热、低旁瓣效应,是肿瘤高效、微创治疗新设备,在一定程度上降低了放疗“大毒”致病的风险。
化疗药物通过多种机制发挥其细胞毒性作用,导致DNA复制和修复受损,对肿瘤细胞的杀伤作用毋庸置疑。但化疗药物具有明显的攻伐属性,伤人正气。李娜等[17]将“性味归经”理论引进化疗药物属性论证,认为顺铂等化疗药物具有苦寒、沉降的特性,这与化疗后人体呈现的一派肃杀之性相契合,机体“阳化气,阴成形”功能受损,人体正常细胞生化不及凋亡,形成一系列生化不足的病理特征,如疲乏、骨髓抑制等。另外,骨髓抑制相关的粒细胞减少性发热,也是由于化疗药物之苦寒,损及气血,阴血不足,阳浮为热所致。化疗药物毒性较大,在一定程度上影响了肿瘤患者本就虚弱的脾胃运化功能,导致胃气上逆而发呕吐。脾胃为气血生化之源,呕吐后进一步加重脾胃负担,化生气血随之受损。正气不足、脏腑损耗、气血阴阳亏虚易导致癌因性疲乏(cancer-related fatigue,CRF)的发生,临床多从“虚劳”论治。团队前期采用自主研发的肿瘤免疫知识图谱工具(checkpoint therapeutic target database,CKTTD)[18],开发出具有健脾益气、养血安神的功效“参百灵颗粒”(人参、白术、茯苓、炙甘草、黄芪、当归、灵芝、苦参),可改善肿瘤患者“毒损气血”的病理状态,缓解乳腺癌综合治疗出现的气血亏虚诸证。
化疗耐药形成是限制化疗疗效的棘手问题,团队前期横断面研究发现“正气亏虚癌毒增殖”与“邪气阻滞药毒不敛”是化疗耐药两种演变规律。机体正虚以脾、肺、肾虚为主,瘤体之毒以气滞、血瘀、痰浊、热邪为主[19]。中医药治疗乳腺癌化疗耐药需注重关口前移,应补脾健中、滋补元气、扶正抗癌,同时调整肿瘤内环境,关注瘀毒、痰毒、郁毒等兼夹病理因素,酌情加入丹参、姜黄、茯苓、陈皮、柴胡等,从而对化疗起到减毒增效的作用,防止化疗耐药。
紫杉类、铂类等抗肿瘤药物达到累积用药剂量后,可引起化疗所致周围神经毒性(chemotherapy-induced peripheral neurotoxicity,CIPN),以四肢远端对称性的疼痛、麻木感为主要症状的周围神经病理性疼痛,类似中医“痹证”,可归为血痹。中医理论认为药毒反应在神经末梢,伤于络脉,病变具有气虚血瘀、络脉痹阻的病理特征。化疗药物毒损气血,气血生化乏源是为虚。《素问·五脏生成篇》曰:“掌受血而能握,指受血而能摄……血凝于肌者为痹,凝于脉者为泣。”血运涩少,推动乏力,不能运载阳气到达肢末,则出现麻木疼痛症状。气不通者为麻,血不通者为木,中西医诊治专家共识[20]中推荐的黄芪桂枝五物汤、通络蠲痹汤、参芪扶正注射液均从益气活血通络角度进行干预。
乳腺癌患者焦虑、抑郁患病率分别高达41.9%[21]与32.2%[22]。气血是涵养神气的物质基础,化疗所致气血衰少,神气失养,与抑郁焦虑状态、睡眠障碍密切相关。国内研究证实,乳腺癌患者中伴有抑郁焦虑情绪占63.31%,其中抑郁患者以肝郁痰凝型最高(占46.94%)、焦虑患者以正虚毒炽型最高(占42.86%)[23],可见郁毒、痰毒、正虚是主要病理因素。以“郁毒”为主,方选柴胡疏肝散加减;以“痰毒”为主,方选温胆汤加减;以“正虚”为主,方选归脾汤合甘麦大枣汤加减。
化疗相关性认知功能障碍(chemotherapy-induced cognitive impairment,CICI)又被称为“化疗脑”,属于中医学“健忘”范畴,其病位在脑,与心肾关系最为密切[24]。CICI病机在于化疗后毒损气血导致的“虚毒互伤”,本虚以心神失养、肾虚髓空为主,兼有肝郁气滞之“郁毒”与毒损脑窍之“痰毒”“瘀毒”。治疗应以养心、益肾、疏肝、祛痰、化瘀为原则。
可见,化疗药物伤及气血生化为先。化疗耐药及相关的疲乏、骨髓抑制、周围神经病理性疼痛、睡眠障碍、抑郁焦虑状态、化疗脑等不良反应均与“毒损气血”相关,临床治疗应注重补益气血、扶正抗癌。
乳腺癌患者中约80%呈激素受体(hormone receptor,HR)阳性[25],内分泌治疗可通过降低雌激素水平,或影响其发挥作用,从而抑制乳腺肿瘤细胞分裂增殖,是乳腺癌重要的辅助治疗方法之一。但内分泌治疗后易出现潮热、汗出、烦躁、抑郁、心悸、失眠、乏力等不良反应[26]。中医学将乳腺癌内分泌治疗期的临床表现归属于“脏躁”“郁证”“心悸”“百合病”等范畴。乳腺癌内分泌治疗易损耗患者的肾精、肾气,肾水不足则水不涵木,肝肾阴虚导致肝疏泄功能失常,而发肝气郁结[27]。气郁化热化火,灼伤阴液,阴虚火旺,久则化火成毒,导致毒热蕴结。可见,乳腺癌内分泌治疗的病理因素与“肝肾阴虚”“气郁”“热毒”相关。内分泌治疗尤其是芳香化酶抑制剂(aromatase inhibitors,AIs)可增加乳腺癌患者骨丢失和骨质疏松风险,诱发一系列骨关节症状,包括骨关节疼痛、僵硬、肌痛等。中医归属“骨痹”范畴,诊疗共识中医内治法应重在调理肝肾[28]。
肿瘤局部肿块是邪气聚集的表现,手术治疗与中医祛邪散结的方剂类似[29]。术前患者的正虚主要体现在经络上,脏腑未虚或者虚证不明显,而手术本身会损伤人体正气及气血,会使实证减轻甚至消失,以及虚证的急性加重。曹阳等[30]发现术后局部实邪减少,虚证增多,阳虚、气虚更为显著,可见手术对原有病机产生了影响。且又有“女子乳头属肝,乳房属胃”之说,所以乳腺癌手术易伤胃气。手术造成的气血损伤在术后会逐渐恢复,但脾胃作为后天之本,胃气受损后会导致纳运不调,从而影响脾胃的恢复甚至加重脾胃的损伤。司徒红林等[31]通过聚三类分析发现,术前中医证型以肝郁、痰凝、血瘀最常见,而术后以脾胃虚弱、湿困脾胃为常见,总体是由实证走向虚证。可见,“实去虚存”是乳腺癌术后的核心病机,尤以脾胃亏虚最为主要,中医治疗应顾护脾胃。
手术能很好地解决局部的实体肿瘤,能有效清除痰、瘀、毒等病理因素,但是手术后仍然面临着复发转移的风险。这与“余毒未清”相关,但除了“余毒”的内在条件外,正气内虚亦是复发转移的重要原因。若正气充足,便无邪气停留之所,毒则无以生。王文萍等[32]提出“痰毒流注”病机假说,认为肿瘤及肿瘤术后正气亏虚、痰湿内生,并与残留之余毒互结,痰毒流注经络、脏腑,络脉损伤,气血离络,留而为瘀,而至转移。可见,“正气内虚、余毒流注”是乳腺癌复发转移的核心病机,又因脾为生痰之源,肺为贮痰之器,尤以肺脾气虚及痰毒流注为主,治疗需扶正清源,截毒传舍。
乳腺癌“郁毒致虚”理论是刘彩刚教授的学术思想,是中医乳腺癌临床辨治体系的重要一环,也是乳腺癌发生发展的关键。其中“郁毒搏结、癌毒蔓生、因癌致虚、虚毒互伤”是乳腺癌的核心病机。根据放疗、化疗、内分泌治疗中出现的“热毒伤阴”“毒损气血”“虚火郁热”等的核心病机,刘彩刚教授采用团队自主研发的中药现代化研发工具——肿瘤免疫知识图谱CKTTD,创建了“中药现代化研创体系”,挖掘抗肿瘤优势中药,开展中西医联合攻关,研发了一系列覆盖癌因性疲乏、化疗耐药等方面的特色组方,并通过开展一系列大样本、多中心、随机对照研究,对乳腺癌患者进行全周期、多阶段的管理,形成了“高效、低毒、个体化”的乳腺癌诊疗策略。依托CKTTD研发出的医疗机构制剂参百灵颗粒,疗效获得了国资委、发改委和中医药管理局的高度认可,作为新药处于CDE临床研究阶段,相信未来会有更多的针对乳腺癌及综合治疗后不良反应的药物问世,让其“不但活得长,而且活得好”,助力“健康中国2030”规划。
  • 国家自然科学基金项目(82373063)
  • 辽宁省科技计划项目-辽宁省科技计划联合计划(基金)项目(面上项目)(2023-MSLH-193)
  • 辽宁省肿瘤中医药多学科交叉创新团队项目(LNZYYCXTD-JCCX-001)
  • 沈阳市公共卫生科技专项(公共卫生研发医工结合项目)(22-321-32-18)
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2025年第43卷第7期
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doi: 10.13193/j.issn.1673-7717.2025.07.013
  • 首发时间:2026-10-30
  • 出版时间:2025-07-10
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基金
国家自然科学基金项目(82373063)
辽宁省科技计划项目-辽宁省科技计划联合计划(基金)项目(面上项目)(2023-MSLH-193)
辽宁省肿瘤中医药多学科交叉创新团队项目(LNZYYCXTD-JCCX-001)
沈阳市公共卫生科技专项(公共卫生研发医工结合项目)(22-321-32-18)
作者信息
    1.中国医科大学附属盛京医院,辽宁 沈阳 110004
    2.辽宁省肿瘤中医药多学科交叉创新团队,辽宁 沈阳 110004
    3.辽宁中医药大学,辽宁 沈阳 110847
    4.首都医科大学附属北京中医医院,北京 100010
    5.辽宁中医药大学附属医院,辽宁 沈阳 110032
    6.华润三九医药股份有限公司,广东 深圳 518110

通讯作者:

刘彩刚(1981-),男,山东潍坊人,教授,博士研究生导师,博士,研究方向:中西医结合防治肿瘤。E-mail:。
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https://castjournals.cast.org.cn/joweb/zhzyyxk/CN/10.13193/j.issn.1673-7717.2025.07.013
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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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