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1.河北中医学院,石家庄 050090
2.络病研究与创新中药国家重点实验室,石家庄 050035
3.南京中医药大学,南京 210029
4.河北以岭医院,石家庄 050091
王康,在读博士,从事心血管疾病研究,E-mail:1337206411@qq.com
* 贾振华,博士,主任医师,博士生导师,从事心血管疾病研究,E-mail:jiatcm@163.com
收稿日期:2021-03-01,
网络出版日期:2021-06-09,
纸质出版日期:2021-08-20
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王康,李雅文,常丽萍等.脉络学说理论分析不稳定型心绞痛医案证治规律及网络药理学机制分析[J].中国实验方剂学杂志,2021,27(16):167-176.
WANG Kang,LI Ya-wen,CHANG Li-ping,et al.Rules of Syndrome and Treatment of Unstable Angina Pectoris Guided by Vessel-collateral Theory and Mechanism Analysis Based on Network Pharmacology[J].Chinese Journal of Experimental Traditional Medical Formulae,2021,27(16):167-176.
王康,李雅文,常丽萍等.脉络学说理论分析不稳定型心绞痛医案证治规律及网络药理学机制分析[J].中国实验方剂学杂志,2021,27(16):167-176. DOI: 10.13422/j.cnki.syfjx.20211017.
WANG Kang,LI Ya-wen,CHANG Li-ping,et al.Rules of Syndrome and Treatment of Unstable Angina Pectoris Guided by Vessel-collateral Theory and Mechanism Analysis Based on Network Pharmacology[J].Chinese Journal of Experimental Traditional Medical Formulae,2021,27(16):167-176. DOI: 10.13422/j.cnki.syfjx.20211017.
目的
2
以脉络学说营卫理论为指导系统分析整理不稳定型心绞痛(UAP)现代医案,探析UAP证治规律,并利用网络药理学对证治规律中核心药对治疗UAP的分子机制进行分析。
方法
2
通过PubMed,中国期刊全文数据库(CNKI),万方数据库(Wanfang Data),维普数据库(VIP),中国生物医学文献服务系统(SinoMed)数据库检索自建库至2020年11月所有中药复方治疗UAP相关医案,基于脉络学说营卫理论医案证候判定标准对医案进行证候判定,运用频数统计、系统聚类分析,FP-Growth加强关联分析等数据挖掘方法挖掘UAP证治规律,并利用网络药理学对证治规律中核心药对治疗UAP的分子机制进行分析。
结果
2
研究显示UAP高频证候前4位依次为络气虚滞、瘀血阻络、络气郁滞及痰浊阻络,高频药物有丹参、甘草、川芎、黄芪等,主要药物以化瘀通络、益气固卫、理气解郁及祛痰通络药为主;药物关联规则得到UAP治疗核心药对丹参-川芎-黄芪;药物系统聚类共得到4组药物组合;网络药理学分析显示核心药对丹参-川芎-黄芪治疗UAP的关键成分有槲皮素、木犀草素、丹参酮Ⅱ
A
等,其中关键靶点有丝氨酸/苏氨酸蛋白激酶B1(Akt1),丝裂原活化蛋白激酶1(MAPK1),Jun,白细胞介素-6(IL-6),丝裂原活化蛋白激酶8(MAPK8)。京都基因与基因组百科全书(KEGG)通路分析显示磷脂酰肌醇-3激酶-丝氨酸/蛋白激酶B(PI3K/Akt)信号通路可能是其发挥治疗作用的主要途径。
结论
2
UAP以络气虚(郁)滞、痰瘀阻络为基本病机;治疗以益气化瘀通络为基本治法,兼以理气化痰通络;核心药对丹参-川芎-黄芪治疗UAP的机制具有多成分、多靶点、多通路特点,研究结果为后续脉络学说指导UAP相关分子水平研究提供了思路。
Objective
2
Guided by nutrient-defense stages in the vessel-collateral theory, the modern medical cases of unstable angina pectoris(UAP) were systematically collated and analyzed to explore the rules of syndrome and treatment of UAP and the molecular mechanism of core Chinese herbal combination in the treatment of UAP based on network pharmacology.
Method
2
All medical cases with UAP treated by Chinese medicinal compounds were retrieved from PubMed,China National Knowledge Infrastructure (CNKI),Wanfang Data, VIP, and SinoMed published between database inception and November 2020. The syndromes of medical cases were determined based on the nutrient-defense stages of the vessel-collateral theory. Rules of syndrome and treatment of UAP were investigated by data mining methods, such as frequency statistics, cluster analysis, and enhanced FP-Growth algorithm. The molecular mechanism of core Chinese herbal combination in the treatment of UAP was analyzed by network pharmacology.
Result
2
The first four syndromes of UAP with high frequencies were deficiency and stagnation of collateral Qi, blood stasis obstructing collaterals, depression and stagnation of collateral Qi, and turbid phlegm obstructing collaterals. The Chinese herbal medicines with high frequencies included Salviae Miltiorrhizae Radix et Rhizoma, Glycyrrhizae Radix et Rhizoma, Chuanxiong Rhizoma, and Astragali Radix, which were effective in resolving stasis, dredging collaterals, replenishing Qi, consolidating defensive Qi, regulating Qi, relieving depression, and dispelling phlegm. The association analysis indicated that the core Chinese herbal combination in the treatment of UAP was Salviae Miltiorrhizae Radix Chuanxiong Rhizoma-Astragali Radix. Four Chinese herbal combinations were obtained by cluster analysis. As revealed by network pharmacology, the key components of Salviae Miltiorrhizae Radix et Rhizoma-Chuanxiong Rhizoma-Astragali Radix in the treatment of UAP included quercetin, luteolin, and tanshinone Ⅱ
A
, and the key targets included serine/threonine-protein kinase 1 (Akt1), mitogen-activated protein kinase 1 (MAPK1), Jun, interleukin (IL)-6, and MAPK8. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) signaling pathway might serve as the main pathway for its therapeutic efficacy.
Conclusion
2
The basic pathogenesis of UAP is deficiency/depression and stagnation of collateral qi and turbid phlegm obstructing collaterals. The treatment should follow the principles of replenishing Qi, resolving stasis, and dredging collaterals, assisted with regulating Qi and resolving phlegm. The therapeutic efficacy of Salviae Miltiorrhizae Radix-Chuanxiong Rhizoma-Astragali Radix was achieved via multi-component, multi-target, and multi-pathway. This study is expected to inspire future UAP-related studies at the molecular level based on vessel-collateral theory.
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