目的: 基于数据挖掘和网络药理学方法分析治疗乙肝肝硬化的核心药对及其分子生物学机制。方法: 检索中国知网、万方数据库和维普科技期刊2000年1月至2022年12月所有应用中医药治疗乙肝肝硬化相关的文献,对符合标准的处方进行用药规律的研究,将得出的常用核心药对进行药理分析,预测出活性成分、主要靶点、作用通路等,最后在计算机上采用分子对接技术模拟验证。结果: 筛选出治疗乙肝肝硬化方剂275首,分析得出中药治疗乙肝肝硬化的常用药物有黄芪、丹参等13种,核心组合模式28组,发现槲皮素、木犀草素、山柰酚等成分是核心药对治疗乙肝肝硬化的主要成分,涉及丝氨酸/苏氨酸蛋白激酶1(protein kinase B, AKT1)、肿瘤坏死因子(tumor necrosis factor, TNF)、肿瘤蛋白P53(tumor protein p53, TP53)、白介素-6(Interleukin-6, IL-6)、血管内皮生长因子A(vascular endothelial growth factor A, VEGFA)、半胱氨酸蛋白酶3(Caspase-3, CASP3)等核心靶点和磷脂酰肌醇3-激酶/蛋白激酶(phosphatidylinositol-3-kinase/protein kinase, PI3K/Akt)、TNF、白介素-17(Interleukin-17, IL-17)等信号通路。结论: 乙肝肝硬化的治疗原则是扶正消积,运用数据挖掘得到核心药对“黄芪-丹参”,可以通过干预PI3K-Akt、TNF、IL-17等信号通路发挥调控细胞生长、增殖和存活与炎性反应等作用,从而达到延缓乙肝肝硬化病变进展的目的。
Objective: To analyze the core drug pairs and their molecular biological mechanisms for the treatment of hepatitis B cirrhosis based on data mining and network pharmacology. Methods: Retrieve all the literatures related to the application of traditional Chinese medicine in the treatment of hepatitis B cirrhosis from January 2000 to December 2022 in China National Knowledge Infrastructure, Wanfang Database and VIP Science and Technology Journal, and study the medication rules of the prescriptions that meet the standards. The commonly used core drug pairs were subjected to pharmacological analysis, and the active components, main targets, and action pathways were predicted. Finally, molecular docking technology was used to simulate and verify on the computer. Results: A total of 275 prescriptions for the treatment of hepatitis B cirrhosis were screened. The analysis showed that TCM for the treatment of hepatitis B cirrhosis included 13 kinds of drugs such as Huangqi and Danshen. The core combination mode was 28 groups. Quercetin,Luteolin,Kaempferoland other ingredients were found as the main components of core prescription drugs for the treatment of hepatitis B cirrhosis,involving core targets such as serine/threonine protein kinase 1 (AKT1), tumor necrosis factor (TNF), tumor protein p53 (TP53), interleukin-6 (IL-6), vascular endothelial growth factor A (VEGFA), Caspase-3 (CASP3) and phosphatidylinositol-3-kinase/protein kinase (PI3K/Akt), TNF, interleukin-17 (Interleukin-17). Conclusion: The treatment principle of hepatitis B cirrhosis is to strengthen the body and relieve masses. "Huangqi-Danshen" can play a role in regulating cell growth, proliferation, survival and inflammatory reaction by interfering with PI3K-Akt, TNF, IL-17 and other signal pathways, so as to delay the progression of liver cirrhosis in hepatitis B.
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