Article(id=1322923327060312618, tenantId=1146029695717560320, journalId=1255847919539208197, issueId=1322923011518628427, articleNumber=null, orderNo=null, doi=10.13193/j.issn.1673-7717.2025.03.018, 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=1793339099898, onlineDateStr=2026-10-30, pubDate=1741536000000, pubDateStr=2025-03-10, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1793339099898, onlineIssueDateStr=2026-10-30, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1793339099898, creator=13701087609, updateTime=1793339099898, updator=13701087609, issue=Issue{id=1322923011518628427, tenantId=1146029695717560320, journalId=1255847919539208197, year='2025', volume='43', issue='3', pageStart='1', pageEnd='258', issueExtLink='null', onlineDate='null', pubDate='1741536000000', pubDateStr='2025-03-10', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=0, createTime=1793339024666, creator='13701087609', updateTime=1793340602374, updator='13701087609', preIssue=null, nextIssue=null, articleTotal=null, ext={EN=IssueExt(id=1322929628976906432, tenantId=1146029695717560320, journalId=1255847919539208197, issueId=1322923011518628427, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1322929628981100737, tenantId=1146029695717560320, journalId=1255847919539208197, issueId=1322923011518628427, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null, downloadFileDto=null}, startPage=107, endPage=111, ext={EN=ArticleExt(id=1322923327425217067, articleId=1322923327060312618, tenantId=1146029695717560320, journalId=1255847919539208197, language=EN, title=Research Progress of Chinese Drug Pair in Treatment of Hepatocellular Carcinoma, columnId=1256183361521967297, journalTitle=Chinese Archives of Traditional Chinese Medicine, columnName=Target on National Project, runingTitle=null, highlight=null, articleAbstract=

Hepatocellular carcinoma(HCC)has a high degree of malignancy and poor prognosis,and the current treatment methods have not achieved ideal efficacy. HCCbelongs to the categories of “jaundice”,“accumulation”,“abdominal mass” and “tympania” in traditional Chinese medicine(TCM),and TCM syndrome differentiation and treatment has unique advantages in treatment on HCC. As the core of TCM compound,the research value of Chinese drug pair is of great significance to clinical drug guidance. Studies have found that some drug pairs can relieve clinical symptoms such as abdominal pain,bloating,fatigue and poor appetite,reduce TCM symptom scores,and improve patients'quality of life and prognosis. Pharmacological studies have found that the drug pair has a synergistic and detoxifying effect after combination,and can treat HCCby inhibiting tumor cell proliferation,invasion and migration,blocking cell cycle,and inducing apoptosis and other multi-target ways. Therefore,this paper summarized the efficacy,pharmacological research and clinical application of some “drug pairs” in the treatment of HCC,in order to provide a theoretical basis for the “drug pairs” in the treatment of HCC and provide clinical reference for the prevention and treatment of HCC by TCM.

, authors=Lin DING1, Ruoyu WANG2, 3, Sihan YIN2, Shuanglin QI4, Jing PENG1, Kewei SUN2, 3, authorsList=Lin DING, Ruoyu WANG, Sihan YIN, Shuanglin QI, Jing PENG, Kewei SUN, authorCompany=null, correspAuthors=Kewei SUN, 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=1322923328515736108, articleId=1322923327060312618, tenantId=1146029695717560320, journalId=1255847919539208197, language=CN, title=中药药对治疗肝癌的研究进展, columnId=1256183362172142382, journalTitle=中华中医药学刊, columnName=国家项目点击, runingTitle=null, highlight=null, articleAbstract=

肝细胞癌(Hepatocellular carcinoma,HCC)恶性程度高,预后差,目前治疗手段未取得理想疗效。中医药辨证施治对肝癌治疗疗效颇佳,具有独特优势。肝癌归属于中医“黄疸”“积聚”“癥瘕”“鼓胀”等范畴,中药药对作为中药复方核心,其研究价值对临床用药指导具有重要意义。研究发现,某些药对在临床上可以缓解患者腹痛、腹胀、疲乏及纳差等临床症状,降低中医症状评分,提高患者生活质量,改善患者预后。药理研究发现,药对配伍后有增效减毒作用,可以通过抑制肿瘤细胞增殖、侵袭、迁移,阻滞细胞周期,诱导凋亡等多途径、多靶点发挥抗肝癌作用。故选取疏肝理气,养血柔肝的柴胡、白芍;清热利湿,泻火解毒的半枝莲、白花蛇舌草;益气活血,化瘀消癥的黄芪、莪术;大补元气,敛阴生津的人参、五味子对其治疗HCC的功效、药理作用及临床应用进行归纳总结,为“药对”治疗HCC提供理论基础,为中医药防治肝癌提供临床参考。

, authors=丁琳1, 王若宇2, 3, 银思涵2, 祁双林4, 彭憬1, 孙克伟2, 3, authorsList=丁琳, 王若宇, 银思涵, 祁双林, 彭憬, 孙克伟, authorCompany=null, correspAuthors=孙克伟, authorNote=

丁琳(1995-),女(回族),湖南凤凰人,博士在读,研究方向:中医药防治肝病。

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孙克伟(1963-),男,湖南桑植人,教授,博士研究生导师,博士,研究方向:中医药防治肝病的临床与基础。E-mail:。
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丁琳(1995-),女(回族),湖南凤凰人,博士在读,研究方向:中医药防治肝病。

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丁琳(1995-),女(回族),湖南凤凰人,博士在读,研究方向:中医药防治肝病。

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中药药对治疗肝癌的研究进展
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丁琳 1 , 王若宇 2, 3 , 银思涵 2 , 祁双林 4 , 彭憬 1 , 孙克伟 2, 3
中华中医药学刊 | 国家项目点击 2025,43(3): 107-111
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中华中医药学刊 |国家项目点击 2025 , 43 (3) : 107 -111
中药药对治疗肝癌的研究进展
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丁琳1, 王若宇2, 3, 银思涵2, 祁双林4, 彭憬1, 孙克伟2, 3
作者信息
  • 1.湖南中医药大学第一中医临床学院,湖南 长沙 410007
  • 2.湖南中医药大学第一附属医院,湖南 长沙 410007
  • 3.湖南中医药大学中医学国内一流建设学科,湖南 长沙 410208
  • 4.湖南中医药大学第二临床附属医院,湖南 长沙 410005
通讯作者:
孙克伟(1963-),男,湖南桑植人,教授,博士研究生导师,博士,研究方向:中医药防治肝病的临床与基础。E-mail:。
作者简介:

丁琳(1995-),女(回族),湖南凤凰人,博士在读,研究方向:中医药防治肝病。

Research Progress of Chinese Drug Pair in Treatment of Hepatocellular Carcinoma
Lin DING1, Ruoyu WANG2, 3, Sihan YIN2, Shuanglin QI4, Jing PENG1, Kewei SUN2, 3
Affiliations
  • 1.The First Clinical College of Chinese Medicine,Hunan University of Chinese Medicine,Changsha 410007,Hunan,China
  • 2.The First Affiliated Hospital of Hunan University of Chinese Medicine,Changsha 410007,Hunan,China
  • 3.The Domestic First-class Discipline Construction Project of Chinese Medicine of Hunan University of Chinese Medicine,Changsha 410208,Hunan,China
  • 4.The Second Affiliated Hospital of Hunan University of Chinese Medicine,Changsha 410005,Hunan,China
出版时间: 2025-03-10 doi: 10.13193/j.issn.1673-7717.2025.03.018
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肝细胞癌(Hepatocellular carcinoma,HCC)恶性程度高,预后差,目前治疗手段未取得理想疗效。中医药辨证施治对肝癌治疗疗效颇佳,具有独特优势。肝癌归属于中医“黄疸”“积聚”“癥瘕”“鼓胀”等范畴,中药药对作为中药复方核心,其研究价值对临床用药指导具有重要意义。研究发现,某些药对在临床上可以缓解患者腹痛、腹胀、疲乏及纳差等临床症状,降低中医症状评分,提高患者生活质量,改善患者预后。药理研究发现,药对配伍后有增效减毒作用,可以通过抑制肿瘤细胞增殖、侵袭、迁移,阻滞细胞周期,诱导凋亡等多途径、多靶点发挥抗肝癌作用。故选取疏肝理气,养血柔肝的柴胡、白芍;清热利湿,泻火解毒的半枝莲、白花蛇舌草;益气活血,化瘀消癥的黄芪、莪术;大补元气,敛阴生津的人参、五味子对其治疗HCC的功效、药理作用及临床应用进行归纳总结,为“药对”治疗HCC提供理论基础,为中医药防治肝癌提供临床参考。

中药药对  /  辨证施治  /  肝细胞癌  /  药理作用  /  临床应用

Hepatocellular carcinoma(HCC)has a high degree of malignancy and poor prognosis,and the current treatment methods have not achieved ideal efficacy. HCCbelongs to the categories of “jaundice”,“accumulation”,“abdominal mass” and “tympania” in traditional Chinese medicine(TCM),and TCM syndrome differentiation and treatment has unique advantages in treatment on HCC. As the core of TCM compound,the research value of Chinese drug pair is of great significance to clinical drug guidance. Studies have found that some drug pairs can relieve clinical symptoms such as abdominal pain,bloating,fatigue and poor appetite,reduce TCM symptom scores,and improve patients'quality of life and prognosis. Pharmacological studies have found that the drug pair has a synergistic and detoxifying effect after combination,and can treat HCCby inhibiting tumor cell proliferation,invasion and migration,blocking cell cycle,and inducing apoptosis and other multi-target ways. Therefore,this paper summarized the efficacy,pharmacological research and clinical application of some “drug pairs” in the treatment of HCC,in order to provide a theoretical basis for the “drug pairs” in the treatment of HCC and provide clinical reference for the prevention and treatment of HCC by TCM.

Chinese medicine pair  /  syndrome differentiation and treatment  /  hepatocellular carcinoma  /  pharmacological research  /  clinical application
丁琳, 王若宇, 银思涵, 祁双林, 彭憬, 孙克伟. 中药药对治疗肝癌的研究进展. 中华中医药学刊, 2025 , 43 (3) : 107 -111 . DOI: 10.13193/j.issn.1673-7717.2025.03.018
Lin DING, Ruoyu WANG, Sihan YIN, Shuanglin QI, Jing PENG, Kewei SUN. Research Progress of Chinese Drug Pair in Treatment of Hepatocellular Carcinoma[J]. Chinese Archives of Traditional Chinese Medicine, 2025 , 43 (3) : 107 -111 . DOI: 10.13193/j.issn.1673-7717.2025.03.018
肝细胞癌是我国最常见的恶性肿瘤之一,全球范围内发病率居第六,病死率居第三[1]。因其起病隐匿、恶性程度高,虽目前治疗手段不断发展,但并未取得理想治疗效果,仍存在着高耐药率、高复发率、高转移率等问题。中医药防治肝癌在临床已有大量实践,对于肝癌的综合治疗发挥着不可替代的作用[2-3]。中医将肝癌归属于“黄疸”“积聚”“癥瘕”“鼓胀”等范畴,认为肝癌早期多以实证为主,随着病程进展,逐渐发展为虚实夹杂,到晚期更是邪盛正极虚,其根本是本虚标实,与血瘀、湿热毒邪等病理因素密切相关。故早期可见肝失疏泄,失于濡养;肝气不舒,肝郁气滞,则可见气机不畅,则湿热毒邪内蕴,可化火伤阴耗气,又可毒邪互结为瘀,瘀毒易耗伤阴血,至晚期则多见气阴两亏。中医药在防治肝癌中疗效确切,治疗常根据患者临床表现症状辨证施治,随证加减[4]。药对又称对药,仅由两味中药组成,构成简单,药效明确,是历代医家的经验总结,具有宝贵的研究价值。近来研究表明,中药药对对抗肝癌治疗疗效颇佳。因此本文通过总结某些药对治疗肝癌的功效、药理作用及临床应用,为临床治疗提供参考。
《格致余论·阳有余阴不足论》中提出:“主闭藏者,肾也;司疏泄者,肝也”。肝主疏泄,调畅气机以助脾胃气机升降,精血津液得以遍布全身。若肝失疏泄,气机不畅,气血津液运化失调,机体正气亏虚,外邪内侵,气血津液输布失调,痰瘀湿毒聚集于肝,易内生癌瘤。肝体阴而用阳,肝血不足,肝失濡养,则会导致肝体失用,进而影响肝的疏泄功能。柴胡味辛、苦,归肝胆经,功于疏肝解郁,和解表里,升阳举陷。《药品化义》云:“柴胡,性轻清,主升散,味微苦,主疏肝。”白芍酸、微寒,入肝经、脾经,功在柔肝止痛,养血调经,平抑肝阳,《本草正义》记载:“补血,益肝脾真阴,而收摄脾气之散乱,肝气之恣横,则白芍。”二者配伍,柴胡辛散,疏肝解郁,调畅气机,使阳气升发;白芍酸收,敛肝和营,使阴血归经。二药合用,一散一收,一气一血,疏肝之中兼敛肝,升阳之中兼敛阴,补肝体而和肝用,使肝气行疏,肝血得补,疏柔相济,动静结合,以发挥肝藏血、主疏泄之功能。
现代药理学表明,柴胡、白芍有效成分能够发挥抗炎、保肝、调节免疫、抗肿瘤作用[5-6]。柴胡的主要化学成分包括皂苷类、黄酮类、多糖、挥发油等,可以通过抑制肿瘤细胞增殖、促进凋亡等方式发挥抗肝癌作用。研究表明,柴胡皂苷d以呈剂量依赖性抑制肝癌细胞HepG2和SMMC-7721增殖,可以下调抗凋亡蛋白B淋巴细胞瘤-2(Bcl-2)的表达,促进凋亡蛋白Bcl-2相关X蛋白(Bax)的表达,从而促进肿瘤细胞凋亡[7]。LI等研究表明柴胡皂苷b2在体内外研究均具有抗血管生成作用,其机制可能与抑制血管内皮生长因子(vascular endothelial growth factor,VEGF)/细胞外信号调节激酶(extracellular-signal-regulated kinase,ERK)/缺氧诱导因子-1α(hypoxia inducible factor-1α,HIF-1α)信号通路活化有关[8]。除此之外,化合物之一槲皮素可以通过多途径诱导肿瘤细胞周期停滞和促进细胞凋亡[9]。白芍的主要成分包括白芍总苷、芍药苷、芍药内酯苷、山柰酚等。研究表明芍药苷可以通过上调细胞因子信号传导抑制因子3(SOCS3)来抑制转录激活因子3(signal transducers and activators of transcription 3,STAT3)/程序性死亡受体-配体1(programmed cell death-Ligand 1,PD-L1)信号传导,从而恢复T细胞敏感性以杀死肿瘤细胞[10]。山柰酚能够增加Bax蛋白表达,上调葡萄糖调节蛋白78(GRP78)、葡萄糖调节蛋白94(GRP94)、蛋白激酶R样内质网激酶(protein kinase R-like endoplasmic reticulum kinase,PERK)、内质网应激活化转录因子6(Activating Transcription Factor 6,ATF6)、C/EBP同源蛋白(C/EBPHomologous Protein,CHOP)等基因表达量,从而通过线粒体途径和ER应激途径诱导HepG2细胞凋亡[11]。李湛全研究发现高浓度白芍总苷可以抑制肝癌细胞HepG2增殖,显著上调微管相关蛋白1轻链3-Ⅱ(microtubule-associated protein 1 light chain 3,LC3-Ⅱ)蛋白和自噬相关蛋白p62的表达,表明其可能是通过参与调控肿瘤细胞自噬发挥抑制作用[12]。柴胡、白芍相配伍可以促进芍药苷溶出增强疗效,也可以产生新的活性成分,二者配伍后具有一定增效减毒作用[13-14]。
柴胡-白芍药对常见于四逆散、柴胡疏肝散、柴芍六君子汤等方剂中,具有疏肝理气、调和肝脾、养血柔肝等作用,临床上广泛应用于抗肝癌的综合治疗。柴胡疏肝散加减在原发性肝癌治疗可明显降低肝癌的复发率和提高患者的1年生存率,并在一定程度上减轻介入治疗给机体造成的肝功能损伤,减轻患者腹痛、腹泻等不良反应,提高患者的生活质量[15];并且能够改善肿瘤患者服用索拉非尼相关性腹泻及胃肠道反应[16]。邬谨鸿发现四逆散加减可以有效提高肝动脉化疗栓塞术后患者CD4+/CD8+等T淋巴细胞亚群,下调患者高尔基体糖蛋白73(GP-73)的表达,表明该方能够有效保护术后患者肝功能,提高机体免疫力[17]。黄东彬等通过予以四逆散加减治疗原发性肝癌患者,能够明显改善患者中医证候和生存质量评分,提高IFN-γ、IL-2表达,恢复机体免疫[18]。
半枝莲味辛、苦,性寒,功在清热解毒化瘀利尿。半枝莲之名始见于《外科正宗》,《本草纲目拾遗》中记载其药效:“性寒、消痈肿、治湿郁水肿”[19]。白花蛇舌草味苦、性寒,功在清热解毒、利湿通淋,最早见于《潮州志·药物志》[20],《广西中药志》中载“治小儿疳积,毒蛇咬伤,癌肿”。随着疾病病程进展,肝胆疏泄不利,气血津液运化失调,气不行则湿邪易生,湿邪久蕴成热,湿热之邪互结于内,湿热癌毒内生。临床上患者多伴有发热、腹胀、黄疸等表现。故半枝莲、白花蛇舌草二者相须为用,功于清热利湿、泻火解毒。
半枝莲、白花蛇舌草配伍已经运用在如肝癌、乳腺癌、前列腺癌等多种肿瘤治疗中,是临床最为常见的抗肿瘤药对。半枝莲主要化学成分包括黄酮类、二萜类、多糖类等[21]。已有研究表明它可以通过抑制肿瘤细胞增殖、诱导凋亡、抗肿瘤转移、抑制血管生成等发挥抗肿瘤作用。研究表明,半枝莲多糖可以抑制H22荷瘤小鼠肿瘤生长[22];半枝莲总黄酮呈剂量依赖性抑制肝癌细胞MHCC97H增殖,可能通过降低基质金属蛋白酶(matrix metallo proteinases,MMP)表达和同时增加组织金属蛋白酶抑制因子(tissue Inhibitor of metallo proteinase,TIMP)表达来降低MHCC97H细胞的转移能力,从而发挥抗肿瘤作用[23]。王单单指出半枝莲活性成分可能通过作用于HIF-1α从而下调VEGFA表达水平,进一步抑制VEGF信号通路,抑制肿瘤血管生成[24]。白花蛇舌草目前分离出的主要成分包括环烯醚萜类、含酸化合物、蒽醌类化合物等[25],化合物其具有抗炎镇痛[26]、抗肿瘤[27-28]、调节机体免疫等作用[29]。半枝莲、白花蛇舌草是防治肝癌常用药对,研究表明,二者配伍使用可以显著抑制肝癌细胞H22,其机制是可以参与调节细胞免疫,上调白介素-2(IL-2)、伽马干扰素(interferon-γ,IFN-γ)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)的表达[30]。刘晓卉则指出二者合用可以明显降低细胞葡萄糖摄取量和乳酸水平,可能通过抑制糖酵解途径发挥抗肿瘤作用,且相比于单味药使用,合用对肿瘤抑制作用更为显著[31],刘瑾等通过半枝莲、白花蛇舌草干预H22荷瘤小鼠,发现较于单味药使用,二者合用显著抑制肿瘤生长,其机制可能与下调Bcl-2蛋白表达,上调Bax蛋白表达诱导细胞凋亡有关[32-33]。
半枝莲、白花蛇舌草作为抗肝癌的常用药对,临床上运用广泛,疗效甚佳。如抗肝癌验方消癌解毒方,半枝莲、白花蛇舌草药对是该方的君药组分,贺雪黛[34]将临床收治的61例肿瘤晚期恶病质患者,随机分成治疗组和对照组,对照组予以正常营养支持治疗,治疗组在对照组基础上加用消癌解毒方,结果发现,治疗组血红蛋白、白蛋白水平高于对照组,且临床乏力、腹胀、厌食等临床症状对照组明显改善,有效地改善患者生活质量。另一项临床研究表明[35],经消癌解毒方治疗后,能明显改善肝癌患者胸胁胀闷、情绪抑郁、咯痰量多、舌紫瘀斑、纳差症状。胡振斌教授中药验方抗癌散结方临床疗效确切,可改善肝癌患者肝动脉化疗栓塞术术后KBS评分及临床疗效,治疗组肝功能、甲胎蛋白、凝血功能改善情况均优于对照组[36]。
中医认为正气亏虚始终贯穿于肝癌发病全程,故在治疗时尤其注重顾护人体正气。肝癌病程日久,早可见肝气不疏,气机郁结,且气不行则血不行,又随着病程进展,湿热毒邪壅滞互结,久之则瘀。因此,除了予以益气药物扶正,还应予以活血化瘀药物破瘀祛邪。故益气活血治法是各医家在临床治疗肝癌常用治法之一。黄芪、莪术配伍源于张锡纯所著《医学衷中参西录》中的理冲汤,功在益气活血祛瘀。黄芪性甘、温,归肺、脾经,功于补气升阳、益气固表,生津养血、行滞通痹。莪术归肝、脾经,擅于行气破血,消积止痛。二者配伍益气活血,化瘀消癥,对气虚血瘀所致肝癌疗效甚佳。
黄芪的主要活性成分包括皂苷、黄酮类化合物和多糖等。现代医学表明黄芪具有保护心脑血管、防治神经系统疾病、缓解肝脏纤维化、提高机体免疫力、抗肿瘤等多种作用[37-38]。用不同浓度的黄芪多糖干预肝癌细胞癌SMMC-7721,能有效抑制肿瘤细胞迁移、侵袭能力,其机制可能通过抑制JAK激酶(janus kinase,JAK)/STAT信号通路活化有关[39]。类黄酮花蕊-7-葡萄糖苷是从黄芪中提取出来的主要生物活性化合物,其可以通过调节Bax、Bcl-2和半胱氨酸蛋白酶-3(Caspase-3)的表达,激活线粒体介导的细胞凋亡,发挥抗肝癌作用[40]。莪术化学成分主要含有两大类,即挥发油类和姜黄素类[41]。莪术醇是从莪术挥发油中分离出来的倍萜类化合物,通过使用不同浓度醇干预肝癌细胞HepG2,发现其可以呈浓度、时间依赖性抑制细胞增殖、侵袭和迁移,可以上调第10号染色体缺失的磷酸酶及张力蛋白同源基因(phosphatase and tensin homologue deleted on chromosome 10,PTEN)蛋白表达,下调磷脂酰肌醇3-激酶(PI3K)、磷酸化蛋白激酶B(p-AKT)蛋白,其作用机制可能是通过抑制PTEN/PI3K信号通路活化有关[42]。研究表明,姜黄素可以通过抑制EGFR及其下游靶点来逆转HCC细胞中的仑伐替尼耐药性,姜黄素联合仑伐替尼对抗肝癌效果更为显著[43]。黄芪、莪术药物配伍后可以通过抗肿瘤血管生成发挥作用[44-45],推测黄芪可增强莪术下调血管生成相关蛋白转化生长因子表达[46]。
《医林改错》中指出:“气无形不能结块,结块者,必有形之血也”,随着医家治疗肝癌经验的不断总结,应用活血化瘀药物治疗肝癌已成为目前治疗肝癌的重要手段。吕良文教授[47]强调,在治疗肝癌应用活血化瘀药物时,要注意调和气血,顾护机体平和,不可一味重用活血祛瘀之药物,反而耗血伤本。因此治疗时予以益气、活血药物互相配伍,既补气活血,又不破血逐瘀。常用黄芪配伍莪术,重用黄芪(60~200 g),疗效甚佳。孙桂芝教授治疗经验方“桃红芪术软肝煎”功在益气活血,软坚散结,有着确切的临床疗效[48]。方中黄芪、莪术配伍起着益气健脾、活血祛瘀之用,能有效改善肝癌患者临床症状,提高患者生活质量。
人参性温,味甘,微苦,归肺、脾经,主大补元气,复脉固脱,补脾益肺、生津养血等,是我国最珍贵的中药材之一。人参首载于《神农本草经》:“味甘,微寒,主五脏,安精神,定魂魄。”五味子《神农本草经》中云:“味酸,温,主益气,逆上气,劳伤羸瘦,补不足,强阴。”二者配伍源于《千金要方》中的生脉散,方中人参大补元气,五味子敛汗生津,具有益气生津复脉之功效。肝癌晚期,正气大亏,脏腑功能衰败,肝病日久,气郁或湿热瘀毒均可化火伤阴耗气,致肝阴亏虚,又肝肾精血同源,遂见肝肾阴虚[49]。
人参药用价值极高,目前研究大多集中于皂苷类、多糖类[50]。人参皂苷Rb1(ginsenoside Rb1,Rb1)属于人参二醇型的皂苷,体外培养人肝癌Huh7细胞,通过不同浓度Rb1干预,可以明显提高细胞凋亡率及线粒体相关自噬蛋白表达。这表明人参皂苷Rb1可通过介导线粒体自噬诱导细胞凋亡抑制肿瘤进展[51]。人参皂苷Rh2(ginsenoside Rh2,Rh2)体外可以抑制Huh-7细胞迁移、侵袭能力及降低与侵袭及上皮间质转化(epithelial-mesenchymal transition,EMT)相关蛋白的表达水平;通过构建H22荷瘤小鼠,发现其能抑制小鼠肿瘤生长,其机制可能与抑制环氧化酶-2(cyclooxygenase-2,COX-2)/前列腺素E2(prostaglandin E2,PGE2)通路活化有关[52]。人参多糖可以通过ERK通路诱导肝癌细胞凋亡,可以将肿瘤细胞阻滞在G0/G1期,抑制肝癌细胞增殖[53-54]。五味子包括木脂素类、黄酮类、挥发油类等化学成分[55],临床已被广泛运用防治各种肝脏疾病[56]。相较于单独使用顺铂,五味子酯乙联合顺铂可以降低耐药肝癌细胞Bel7402 G0/G1期细胞、增加S期细胞,并且下调抗凋亡蛋白Bcl-2表达,诱导肿瘤细胞凋亡[57]。另有研究表明,五味子多糖可以减弱化疗药物毒性作用,增强抗肝癌疗效[58]。运用不同浓度的五味子乙素(5、10、20μmol/L)干预高转移能力的肝癌细胞HCCLM3细胞,结果显示干预组有效地抑制细胞侵袭,并且下调了VEGFA、表皮生长因子(epidermal growth factor,EGF)和成纤维细胞生长因子(basic fibroblast growth factor,bFGF)的表达[59]。二者相配伍使用,五味子中木脂素类成分和人参中活性较强的小分子量皂苷含量均有明显增加,这表明较与单味药使用,二者相须使用能一定程度增强药效功用[60]。
人参、五味子配伍是临床常见药对,临床常见有生脉饮、人参养荣丸、玉泉颗粒等32个方剂,中药注射剂有生脉注射液[61-62]。具有大补元气,敛阴生津复脉之效,多用于肝癌晚期。肝癌晚期,正气亏虚,久病累肾,肝肾精血同源,且瘀毒久攻伤阴耗血,故治疗时多以人参、五味子配伍大补元气,敛阴生津。研究表明人参养荣汤可改善化疗患者的疲乏症状,提高患者生活质量[63]。生脉注射液在临床运用广泛,它可以提高肝癌患者CD3+、CD4+、NK细胞水平和CD4+/CD8+细胞水平,保护肝功能,降低肝损伤[64]。陈荣将收治的原发性肝癌术后患者随机分为治疗组与对照组,对照组予以常规抗感染、止血等对症支持治疗,治疗组于对照组基础上加用生脉注射液,结果表明,生脉注射液能有效改善患者腹胀、气短、疲劳等症状,促进术后恢复,有效缩短住院时间[65]。
药对是中药组方配伍的基本形式,是中药复方组成核心,它不是随意两味中药的叠加,而是历代医家根据临床实践及药性七情理论进行配伍,可以起到协同增效或是制约减毒作用[66]。中药药对使用具有悠久历史,现已广泛应用于抗肝癌治疗。肝藏血,主疏泄,体阴而用阳。肝癌的发生发展与肝主疏泄功能异常密切相关。故针对于此,选用柴胡-白芍以疏肝理气,养血柔肝。肝气郁滞,疏泄不利,气血津液输布失调,湿热毒邪内蕴,故选用白花蛇舌草、半枝莲清热利湿,泻火解毒。久病为瘀,瘀血内阻,故选用黄芪、莪术以行益气活血,化瘀消癥之效。疾病晚期,气阴亏虚,选用人参、五味子,大补元气,敛阴生津。临床研究表明,上述药对可以通过有效改善患者腹胀、疲劳、纳差等临床症状,调节机体免疫力,提高生活质量。现代药理学表明,上述药对可以通过抑制肝癌细胞增殖、诱导细胞凋亡、抑制细胞迁移侵袭、抑制肿瘤血管生成及减轻化疗药物毒性等多途径、多靶点发挥抗肝癌作用。中医中药在防治肝癌颇具优势,药对配伍简单,疗效明确,在临床上也发挥重要作用,具有宝贵研究价值,临床医师在选方用药时应当辨证灵活选用,合理配伍,以期提高临床疗效。
  • 国家自然科学基金青年科学基金项目(82104809)
  • 湖南中医药大学双一流学科建设项目(2018〔03〕)
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2025年第43卷第3期
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doi: 10.13193/j.issn.1673-7717.2025.03.018
  • 首发时间:2026-10-30
  • 出版时间:2025-03-10
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国家自然科学基金青年科学基金项目(82104809)
湖南中医药大学双一流学科建设项目(2018〔03〕)
作者信息
    1.湖南中医药大学第一中医临床学院,湖南 长沙 410007
    2.湖南中医药大学第一附属医院,湖南 长沙 410007
    3.湖南中医药大学中医学国内一流建设学科,湖南 长沙 410208
    4.湖南中医药大学第二临床附属医院,湖南 长沙 410005

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孙克伟(1963-),男,湖南桑植人,教授,博士研究生导师,博士,研究方向:中医药防治肝病的临床与基础。E-mail:。
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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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