摘要
目的:通过网络药理学和分子对接技术研究参麦注射液抑制化疗后白细胞减少的作用机制,并进行临床验证。方法:通过TCMSP和BATMAN-TCM数据库筛选参麦注射液中的化学成分,采用Swisstarget数据库筛选活性成分的作用靶点;利用疾病数据库筛选白细胞减少的相关疾病靶点;取交集靶点后建立“药物-成分-靶点”网络,进行GO功能和KEGG通路富集分析;构建蛋白互作网络分析,选取关键靶点进行分子对接。选取2021年6月至2023年6月在江苏省中医院接受FOLFOX方案化疗的患者60例,随机分为对照组和试验组,每组30例。试验组化疗的同时予以参麦注射液,观察2组给药后白细胞、中性粒细胞、肿瘤坏死因子(TNF-α)、白细胞介素-6(IL-6)水平和人粒细胞刺激因子注射液对症处理率。结果:参麦注射液有效成分59个,药物靶点674个,白细胞减少相关疾病靶点1394个,交集靶点147个;涉及GO功能776个,KEGG通路158条,主要包括癌症通路、AGE-RAGE信号通路、PI3K-Akt信号通路等;PPI网络分析筛选出AKT1、TNF、IL-6等核心靶蛋白,将核心靶点与反向筛选的4个活性成分进行分子对接。临床对照验证结果显示相较于对照组,试验组患者化疗后的白细胞、中性粒细胞绝对值增高,TNF-α、IL-6水平降低(P<0.05),且人粒细胞刺激因子注射液使用率低。结论:参麦注射液通过多成分、多靶点、多通路机制抑制化疗后白细胞减少,并降低血清TNF-α和IL-6水平。
OBJECTIVE To explore the mechanism of Shenmai Injection suppressing leukopenia after chemotherapy through network pharmacology and molecular docking technology and conduct clinical validations.METHODS The chemical components of Shenmai Injection were screened by the databases of TCMSP and BATMAN-TCM.And the database of Swisstarget was utilized for screening for the action targets of active components.Disease databases were utilized for screening the relevant disease targets for leukopenia.After taking intersection targets,“drug-component-target”network was established for GO function and KEGG pathway enrichment analysis.Protein interaction network was constructed and key targets were selected for molecular docking.From June 2021 to June 2023,60 patients on FOLFOX chemotherapy were selected and randomized into two groups of control and trial(n=30 each).In trial group,Shenmai Injection was dosed with chemotherapy.The levels of leukocyte,neutrophil,tumor necrosis factor,interleukin 6 and symptomatic treatment rate of human granulocyte stimulating factor injection were compared between two groups.RESULTS There were 59 active components,674 drug targets,1394 disease targets for leukopenia and 147 intersection targets in Shenmai Injection.It involved 776 GO functions and 158 KEGG pathways of cancer and AGE-RAGE/PI3K-Akt signaling.PPI network visualization analysis revealed core target proteins such as AKT1,TNF,IL-6 and molecular docking of core targets with four active ingredients of reverse screening was performed.As compared with control group,absolute values of leukocytes and neutrophils after chemotherapy spiked and the levels of TNF-α and IL-6 level in trial group(P<0.05).There was a low usage rate of human granulocyte stimulating factor injection.CONCLUSION Shenmai Injection may suppress leukopenia after chemotherapy through a multi-component,multi-target,multi-pathway mechanism.And serum levels of TNF-αand IL-6 are down-regulated.
作者
孙程
任发燕
邵杰
王俊壹
李金昌
谭喜莹
SUN Cheng;REN Fayan;SHAO Jie;WANG Junyi;LI Jinchang;TAN Xiying(Department of Pharmacy,Affiliated Hospital,Nanjing University of Traditional Chinese Medicine,Jiangsu Nanjing 210029,China;Department of Oncology,Affiliated Hospital,Nanjing University of Traditional Chinese Medicine,Jiangsu Nanjing 210029,China;Department of Laboratory Medicine,Affiliated Hospital,Nanjing University of Traditional Chinese Medicine,Jiangsu Nanjing 210029,China)
出处
《中国医院药学杂志》
CAS
北大核心
2024年第17期1987-1993,2007,共8页
Chinese Journal of Hospital Pharmacy
基金
南京药学会-常州四药医院药学科研基金项目(编号:2020YX004)。
