[1]熊志刚,杨淑莲,李圣豪,等.杨淑莲辨治白血病的方药规律及核心药物作用机制的网络药理学研究[J].南京师大学报(自然科学版),2026,49(01):65-82.[doi:10.3969/j.issn.1001-4616.2026.01.008]
 Xiong Zhigang,Yang Shulian,Li Shenghao,et al.Prescription Patterns of Yang Shulian in the Treatment of Leukemia and the Network Pharmacology Study on the Mechanisms of Core Drugs[J].Journal of Nanjing Normal University(Natural Science Edition),2026,49(01):65-82.[doi:10.3969/j.issn.1001-4616.2026.01.008]
点击复制

杨淑莲辨治白血病的方药规律及核心药物作用机制的网络药理学研究()

《南京师大学报(自然科学版)》[ISSN:1001-4616/CN:32-1239/N]

卷:
49
期数:
2026年01期
页码:
65-82
栏目:
生物学
出版日期:
2026-02-10

文章信息/Info

Title:
Prescription Patterns of Yang Shulian in the Treatment of Leukemia and the Network Pharmacology Study on the Mechanisms of Core Drugs
文章编号:
1001-4616(2026)01-0065-18
作者:
熊志刚123杨淑莲2李圣豪4杨 坤15王茂生12何其悦3
(1.河北中医药大学,河北 石家庄 050091)
(2.河北中医药大学附属廊坊市中医医院,河北 廊坊 065099)
(3.廊坊市大厂县疾控中心门诊部,河北 廊坊 065300)
(4.河北医科大学第四医院,河北 石家庄 050011)
(5.湖北中医药大学,湖北 武汉 430065)
Author(s):
Xiong Zhigang123Yang Shulian2Li Shenghao4Yang Kun15Wang Maosheng12He Qiyue3
(1.Hebei University of Chinese Medicine,Shijiazhuang 050091,China)
(2.Langfang Hospital of TCM Affiliated to Hebei University of Chinese Medicine,Langfang 065099,China)
(3.Outpatient Department of Disease Prevention and Control Center of Dachang County,Langfang City,Langfang 065300,China)
(4.The 4th Hospital of Hebei Medical University,Shijiazhuang 050011,China)
(5.Hubei University of Chinese Medicine,Wuhan 430065,China)
关键词:
杨淑莲白血病方药规律网络药理学核心药物作用机制
Keywords:
Yang Shulianleukemiamedication patterns and prescription rulesnetwork pharmacologycore drugsaction mechanisms
分类号:
R28; R289; R273; R733
DOI:
10.3969/j.issn.1001-4616.2026.01.008
文献标志码:
A
摘要:
总结杨淑莲辨治白血病的方药规律,探讨核心药物潜在机制并验证. 收集杨师治疗白血病处方,用中医传承计算平台及SPSS 软件挖掘方药数据,筛选高频中药组合,确定核心药物; 用网络药理学方法提取核心药物有效成分,绘制核心药物-有效成分-关键靶点-信号通路网络,分析其抗白作用机制; 用Vina 1.1.2对接验证核心药物成分与关键靶点结合活性、R studio绘制对接结果热图. 纳入处方176个,涉289味中药,最常用甘草、当归、黄芪,“甘草,黄芪->当归”、“阿胶,墨旱莲->女贞子”组合,性味多甘寒、归肝经; 惯用黄芪、当归、女贞子、熟地黄等益气阴与生地黄、黄芩清热毒,阿胶、三七、仙鹤草化瘀止血,茯苓、白术理气化痰之品合方; 公因子代表药贡献率63.90%,含高频中药; 高频共现网络涉25味药,甘草、当归、黄芪、茯苓、白术、生地黄、熟地黄、女贞子、人参为核心药物,含205个有效成分、243个作用靶点,与该病共有45个关键靶点,前5依次为TP53、STAT3、JUN、AKT1、TNF,与489个生物学过程、12个细胞组分、18个分子功能相关,富集于30条白血病相关信号通路,HTLV-1、PI3K-AKT、MAPK等10条信号通路被证实确有影响,富集了TP53、STAT3、JUN等37个关键靶点; 核心成分β-谷甾醇与前5个关键靶点结合活性良好. 杨师提出白血病病机为邪毒内蕴骨髓、肝肾阴精血虚,应名“髓毒”,宜治益气养阴、清热解毒、化瘀止血,用药治肝为主、肝脾肾同调、兼顾五脏,活用四君子汤、参芪杀白汤益气阴,犀角地黄汤清热毒,护心康散瘀止血,配伍补骨脂、黄精滋阴温阳,川芎、白花蛇舌草解毒散瘀止血; 惯用复方黄黛片救急、益气活血解毒方防复; 核心药物富含的β-谷甾醇主要通过作用于多靶点、多通路,抑制白血病细胞存活、促其凋亡,发挥抗白效应.
Abstract:
To summarize the prescription patterns used by Yang Shulian in treating leukemia,explore the potential mechanism of the key drugs,and verify it. Prescriptions for leukemia treatment by Prof. Yang were collected. Data on herbal formulations were analyzed using the Traditional Chinese Medicine Inheritance Calculation Platform and SPSS software to identify high-frequency herb combinations and determine core drugs. Network pharmacology methods were employed to extract active components of the core drugs and construct a "core drugs-active components-key targets-signaling pathways" network to analyze their anti-leukemia mechanisms. Molecular docking was performed using Vina 1.1.2 to validate the binding affinity between core drug components and key targets,and R Studio was used to generate heatmaps of the docking results. A total of 176 prescriptions involving 289 Chinese herbs were included. The most frequently used herbs were Gancao(Glycyrrhiza uralensis),Danggui(Angelica sinensis),and Huangqi(Astragalus membranaceus). Key herb combinations included “Gancao+Huangqi → Danggui” and “Ejiao(Donkey-hide Gelatin)+Mohanlian(Eclipta prostrata)→ Nüzhenzi(Ligustrum lucidum).” Herbs were predominantly sweet and cold in nature,primarily acting on the Liver Meridian. Common combinations included Huangqi,Danggui,Nüzhenzi,and Shudihuang(Rehmannia glutinosa)for supplementing Qi and nourishing Yin; Shengdihuang(Rehmannia glutinosa)and Huangqin(Scutellaria baicalensis)for clearing heat and toxin; Ejiao,Sanqi(Panax notoginseng)and Xianhecao(Agrimonia pilosa)for resolving stasis and stopping bleeding; Fuling(Poria cocos)and Baizhu(Atractylodes macrocephala)for regulating Qi and resolving phlegm. Common factor analysis indicated that representative herbs contributed 63.90% of the variance,encompassing high-frequency herbs. A high-frequency co-occurrence network involved 25 herbs,with Gancao,Danggui,Huangqi,Fuling,Baizhu,Shengdihuang,Shudihuang,Nüzhenzi,and Renshen(Panax ginseng)identified as core drugs. These contained 205 active components and 243 target proteins,with 45 key targets overlapping with leukemia-related genes. The top 5 targets were TP53,STAT3,JUN,AKT1,and TNF. These were associated with 489 biological processes,12 cellular components,and 18 molecular functions,and were enriched in 30 leukemia-related signaling pathways. Ten pathways,including HTLV-1,PI3K-AKT,and MAPK,were confirmed to be significantly involved,enriching 37 key targets such as TP53,STAT3 and JUN. The core component β-sitosterol exhibited strong binding affinity with the top five key targets. Prof. Yang proposed that the pathogenesis of leukemia involves internal accumulation of pathogenic toxins in the bone marrow and deficiency of Yin,essence,and blood in the liver and kidney,which should be termed “marrow toxin”. Treatment should focus on supplementing Qi and nourishing Yin,clearing heat and detoxifying,and resolving stasis to stop bleeding. Herbal strategies prioritize treating the liver while simultaneously regulating the liver,spleen,and kidney,with attention to all five zang organs. Commonly used formulas include Sijunzi decoction for boosting Qi and Shenqi Shabai Decoction for nourishing Yin; Xijiao Dihuang Decoction for clearing heat and toxin; Huxin Kang for dissipating stasis and stopping bleeding; combinations such as Buguzhi(Psoralea corylifolia)and Huangjing(Polygonatum sibiricum)to nourish Yin and warm Yang,as well as Chuanxiong(Ligusticum chuanxiong)and Baihuasheshecao(Hedyotis diffusa)for detoxifying,dissipating stasis,and stopping bleeding. Compound Huangdai Tablets are often used for emergency treatment,while Yiqi Huoxue Jiedu Formula is employed to prevent relapse. The core drugs are rich in β-sitosterol,which exerts significant anti-leukemia effects by inhibiting leukemia cell survival and promoting apoptosis through multiple targets and pathways.

参考文献/References:

[1]张之南,沈悌. 血液病诊断及疗效标准[M]. 3版. 北京:科学出版社,2007.
[2]杨淑莲.杨淑莲中医血液病学术集验[M]. 哈尔滨:黑龙江科学技术出版社,2020.
[3]杨丽,彭瑞,叶晓雯. 1990—2019年中国白血病归因于各类危险因素的疾病负担分析与模型预测[J]. 现代预防医学,2023,50(2):205-210.
[4]蓝海,侯丽,郎海燕,等. 常见血液病的中医分类与命名[J]. 中医杂志,2019,60(9):750-753.
[5]王茂生,李君,杨淑莲. 髓毒(白血病)中医诊疗辑要[J]. 中国中医急症,2012,21(12):1969-1970.
[6]杨淑莲,王茂生.血液病中医治验心悟[M]. 北京:人民军医出版社,2014.
[7]国家药典委员会.中华人民共和国药典(四部):2020年版[M]. 北京:中国医药科技出版社,2020.
[8]南京中医药大学. 中药大辞典[M]. 2版. 上海:上海科学技术出版社,2014.
[9]杨洪军,唐仕欢,卢朋. 中医传承辅助平台的开发与应用[M]. 福州:福建科学技术出版社,2013.
[10]颜艳,王彤. 医学统计学[M]. 5版. 北京:人民卫生出版社,2020.
[11]张浩彬,周伟珠. IBM SPSS Modeler 18.0数据挖掘权威指南[M]. 北京:人民邮电出版社,2019.
[12]李梢. 网络药理学[M]. 北京:清华大学出版社,2022.
[13]Hsin K Y,Ghosh S,Kitano H. Combining machine learning systems and multiple docking simulation packages to improve docking prediction reliability for network pharmacology[J]. PLoS One,2013,8(12):e83922.
[14]赵佶敕. 圣济总录校注 上[M]. 上海:上海科学技术出版社,2016.
[15]张仲景. 金匮要略[M]. 北京:中医古籍出版社,1997.
[16]薛己. 薛氏医案[M]. 北京:中国中医药出版社,1997.
[17]陶弘景,尚志钧. 名医别录辑校本[M]. 北京:中国中医药出版社,2013.
[18]甄权,尚志钧. 药性论[M]. 合肥:安徽科学技术出版社,2006.
[19]寇宗奭. 本草衍义[M]. 北京:中国医药科技出版社,2018.
[20]张锡纯. 医学衷中参西录 上[M]. 郑州:河南科学技术出版社,2021.
[21]汪绮石. 理虚元鉴[M]. 北京:中国医药科技出版社,2018.
[22]汪昂. 医方集解[M]. 北京:中国医药科技出版社,2011.
[23]周礼达. 泉州本草彩色图谱[M]. 天津:天津科学技术出版社,2018.
[24]赵以德衍义. 金匮玉函经二注[M]. 北京:人民卫生出版社,1990.
[25]张元素. 医学启源[M]. 北京:中国中医药出版社,2019.
[26]吴昆. 医方考[M]. 北京:人民卫生出版社,2007.
[27]宋太医局. 太平惠民和剂局方[M]. 北京:中国中医药出版社,2020.
[28]傅大治,傅华洲. 四君子汤防治白血病研究进展[J]. 浙江中西医结合杂志,2013,23(10):866-868.
[29]罗美. 古今名医方论[M]. 北京:中国中医药出版社,2007.
[30]张丽敏. 香砂六君子汤合当归补血汤治疗急性白血病化疗后不良反应的临床观察[D]. 武汉:湖北中医药大学,2015.
[31]刘俊. 常见病名医秘验良方[M]. 2版. 北京:化学工业出版社,2022.
[32]孙思邈. 备急千金要方[M]. 北京:中国医药科技出版社,2011.
[33]龙石峰. 中药犀角地黄汤加减疗法对急性白血病发热患者的退热作用评价[J]. 抗感染药学,2016,13(4):917-918.
[34]张仲景. 伤寒论[M]. 南宁:广西科学技术出版社,2015.
[35]乔曦,许世豪,王宇炜,等. 大柴胡汤通过调控p38 MAPK/IL-6/STAT3信号通路抑制肝癌的作用机制[J]. 中国实验方剂学杂志,2022,28(16):19-31.
[36]袁惠,黄昌锐,喻正科,等. 护心康片通过VEGF/VEGFR-2信号通路影响ApoE-/-小鼠动脉粥样硬化斑块的实验研究[J]. 中国中医急症,2023,32(6):963-968.
[37]张山雷. 本草正义[M]. 太原:山西科学技术出版社,2013.
[38]卢多逊. 《开宝本草》辑校[M]. 北京:北京科学技术出版社,2019.
[39]唐容川. 血证论[M]. 北京:中国医药科技出版社,2020.
[40]李时珍. 本草纲目[M]. 武汉:崇文书局,2008.
[41]吴仪洛. 本草从新[M]. 太原:山西科学技术出版社,2015.
[42]张璐. 本经逢原[M]. 北京:中医古籍出版社,2017.
[43]倪朱谟. 本草汇言[M]. 上海:上海科学技术出版社,2005.
[44]赵学敏. 本草纲目拾遗[M]. 北京:中国中医药出版社,2007.
[45]张景岳. 景岳全书[M]. 太原:山西科学技术出版社,2006.
[46]王晓波,黄世林. 复方黄黛制剂临床与作用机理[M]. 北京:北京科学技术出版社,2011.
[47]常敏毅. 日华子本草辑注[M]. 北京:中国医药科技出版社,2016.
[48]王茂生,杨淑莲,侯伟,等. 益气解毒活血方联合化疗对成人急性髓细胞白血病患者生存质量的影响[J]. 中国中医急症,2007(11):1330-1331.
[49]王雍,王志龙,衣凯宁,等. HTLV-1病毒蛋白Tax和HBZ协同促进成人T细胞白血病发生的机制[J]. 病毒学报,2019,35(1):149-157.
[50]周云龙,林智敏,易小玉,等. PI3K/Akt信号通路调控急性髓系白血病机制及中医药治疗研究进展[J]. 中国现代医学杂志,2024,34(13):63-70.
[51]李慧,张吴霞,熊烨. 欧前胡素调节MAPK/mTOR/p70S6K信号通路对急性髓系白血病细胞恶性生物学行为的影响[J]. 河北医药,2023,45(13):1941-1945.
[52]陈瑜,陶石,胡敏,等. 槲皮素对白血病细胞增殖、凋亡的影响[J]. 中国老年学杂志,2024,44(3):688-691.
[53]朱志明,王娟娟,王苏美,等. 山柰酚抗肿瘤作用的药理研究进展[J]. 中药新药与临床药理,2024,35(3):445-452.
[54]赵冰洁,车虹,胡琏,等. β-谷甾醇通过诱导ROS累积造成氧化应激抑制K562/ADR细胞增殖并促进凋亡和分化[J]. 现代肿瘤医学,2024,32(4):641-645.
[55]袁长威,熊媛媛,张青兰,等. 芒柄花黄素对白血病HL-60细胞增殖、凋亡和miR-21/PTEN/AKT信号通路的影响[J]. 现代肿瘤医学,2020,28(7):1062-1066.
[56]韩萍萍,王怀宇,蔡云,等. 甘草查尔酮A对HL-60细胞恶性生物学行为的抑制作用及其机制[J]. 山西医科大学学报,2024,55(6):689-697.
[57]Wen D,Xiao H,Gao Y,et al. N6-methyladenosine-modified SENP1,identified by IGF2BP3,is a novel molecular marker in acute myeloid leukemia and aggravates progression by activating AKT signal via de-sumoylating HDAC2[J]. Molecular Cancer,2024,23(1):116.
[58]Liang D,Wang Q,Zhang W. JAK/STAT in leukemia:a clinical update[J]. Molecular Cancer,2024,23(1):25.
[59]Carter J L,Hege K,Yang J,et al. Targeting multiple signaling pathways:the new approach to acute myeloid leukemia therapy[J]. Signal Transduction Targeted Therapy,2020,5(1):288.
[60]Litzow M R,Ferrando A A. How I treat T-cell acute lymphoblastic leukemia in adults[J]. Blood,2015,126(7):833-841.

备注/Memo

备注/Memo:
收稿日期:2025-04-30.
基金项目:全国名老中医传承工作室建设项目(国中医药人教函[2022]75号)、中国民族医药学会科研项目(2022Z1088-480601)、第五批全国中医临床优秀人才研修项目(国中医药人教函[2022]1号).
通讯作者:王茂生,教授,主任中医师,研究方向:中西医结合血液病诊治研究. E-mail:wms65352003@163.com
更新日期/Last Update: 2026-02-10