基于网络药理学解析冠心宁片抗血栓及新冠病毒引起的微血栓的潜在机制  

Analysis of the mechanisms of Guanxinning Tablet for antithrombotic and microthrombotic effects caused by COVID-19 based on network pharmacology

作　　者：公佩钰 肖光旭 李文君 樊官伟[1,2] 吕明[1] 朱金墙[1] GONG Pei-yu;XIAO Guang-xu;LI Wen-jun;FAN Guan-wei;LU Ming;ZHU Jin-qiang(State Key Laboratory of Component-based Chinese Medicine,Tianjin University of Traditional Chinese Medicine,Tianjin 301617,China;National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion,the First Teaching Hospital of Tianjin University of Traditional Chinese Medicine,Tianjin 300193,China)

机构地区：[1]天津中医药大学,组分中药国家重点实验室,天津301617 [2]天津中医药大学第一附属医院,国家中医针灸临床医学研究中心,天津300193

出　　处：《药学学报》2024年第9期2545-2555,共11页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金项目(82274436));天津市教委科研计划项目(2023KJ149);正大青春宝药业有限公司技术服务委托项目(QCB-YXB-20220029).

摘　　要：血栓形成是增加新冠肺炎患者死亡率和导致长新冠后遗症的关键因素。由活血化瘀中药丹参、川芎组成的冠心宁片(GXNT)具有显著的抗血栓活性,但其抗常规血栓与由新冠病毒引起微血栓机制之间的异同仍不清楚。本文运用体外抗血小板实验、网络药理学分析、分子对接技术和分子生物学实验,初步揭示了GXNT治疗血栓及新冠病毒引起的微血栓的主要活性成分、潜在靶点和作用机制。体外血小板聚集和黏附实验结果表明,GXNT具有显著的抗血小板聚集和黏附的活性,且呈一定的剂量依赖性。网络药理学分析发现,GXNT中的丹酚酸B、丹参酮IA、咖啡酸和川芎嗪能够通过关键靶点高迁移率族蛋白B1(highmobilitygroupbox1protein,HMGB1)、肿瘤坏死因子(tumor necrosis factor,TNF)、白细胞介素6(interleukin-6,IL6)和丝氨酸/苏氨酸激酶1(AKT serine/threonine kinase1,AKT1)来抗血栓及由新冠病毒引起的微血栓。其中,HMGB1信号通路为其关键的共同机制之一。Western blot实验结果也表明,GXNT对血小板中HMGB1蛋白的表达水平有显著抑制作用。综上,本文探究的GXNT抗常规血栓与由新冠病毒引起微血栓机制之间的异同为临床防治长新冠后遗症提供用药参考和理论依据。该动物实验已通过天津中医药大学实验动物伦理委员会审核批准(编号:TCM-LAEC2023187g1549)。Thrombosis is a key factor that increases the mortality rate of COVID-19 patients and causes long COVID sequelae.Guanxinning Tablet(GXNT),which is composed of Salvia miltiorrhiza and Ligusticum Chuanxiong,has significant antithrombotic activity,but the similarities and differences between its anti-conventional thrombus and microthrombus induced by COVID-19 remain unclear.In this paper,the main active components,potential targets and mechanisms of GXNT in the treatment of thrombus and microthrombus caused by COVID-19 were preliminarily revealed by using anti-platelet experiments in vitro,network pharmacology analysis,molecular docking technology and molecular biology experiments.The results of platelet aggregation and adhesion experiments in vitro showed that GXNT had significant anti-platelet aggregation and adhesion activities in a dose-dependent manner.Using network pharmacology analysis,it was revealed that salvianolic acid B,tanshinone IIA,caffeic acid and ligustrazine in GXNT could resist thrombus and microthrombus caused by COVID-19 through key targets as the high mobility group box 1 protein(HMGB1),tumor necrosis factor(TNF),interleukin 6(IL6)and AKT serine/threonine kinase 1(AKT1).HMGB1 signaling pathway is one of its key common mechanisms.Western blot also indicated that GXNT significantly inhibited the expression of HMGB1 protein in platelets.In summary,this paper explores the similarities and differences between the mechanism of GXNT against conventional thrombus and microthrombus caused by COVID-19 and provides drug reference and theoretical basis for clinical prevention and treatment of long COVID sequelae.The animal experiment has been approved by the Experimental Animal Ethics Committee of Tianjin University of Traditional Chinese Medicine(No.TCM-LAEC2023187g1549).

关 键 词：冠心宁片 抗血栓 COVID-19 长新冠 HMGB1信号通路 

分 类 号：R966[医药卫生—药理学]