摘要
传统中药丹参及其制剂在临床应用范围广泛,对于冠心病(coronary heart disease,CHD)有良好疗效,其脂溶性成分丹参酮ⅡA具有抗动脉粥样硬化、抗心肌缺血、抗心肌纤维化和抑制心肌肥厚等作用,通过作用于Toll样受体/核转录因子-κB(toll like receptor 4/nuclear transcription factor-κB,TLR/NF-κB)、丝裂原活化蛋白激酶(mitogen-activated protein kinase,MAPK)/NF-κB、磷脂酰肌醇3-激酶/蛋白激酶B(phosphoinositide 3-kinase/protein kinase B,PI3 K/AKT)、雷帕霉素靶蛋白/内皮型一氧化氮合酶(mammalian target of rapamycin/endothelial nitric oxide synthase,mTOR/eNOS)、转化生长因子-β1(transforming growth factor-β1,TGF-β1)/Smad2/3、应激激活蛋白激酶(stressac-tivated pro-tein kinase,SAPK)/MAPK、胞外信号调节蛋白激酶(extracellular regulated protein kinases,ERK)/核转录因子红细胞系2相关因子2(nuclear factor erythroid-2-related factor 2,Nrf2)、胱抑素C/Wnt(cystatin C/Wnt,Cys-C/Wnt)等信号转导通路发挥效应;隐丹参酮通过抑制炎性介质预防早期冠脉粥样硬化。水溶性成分丹酚酸A通过调节PI3 K/Akt、丝氨酸/苏氨酸激酶(serine/threonine kinase,GSK-3β)、c-Jun氨基末端激酶(c-Jun N-terminal kinase,JNK)和ERK1/2等通路抑制心肌细胞凋亡,降低炎症水平,改善心肌梗死;丹酚酸B通过抑制TLR4和核苷酸结合寡聚化结构域样受体蛋白3(nucleotide-binding oligomerization domain-like receptor protein 3,NLRP3)炎性体表达减轻心肌损伤;丹参素通过抑制Janus酪氨酸蛋白激酶(janus tyrosine protein kinase,JAK)/信号转导及转录激活因子(signal transduction and transcriptional activator,STAT)信号通路改善微循环、抗炎抗氧化、抗内皮损伤和抗血小板聚集。丹参水溶性成分制剂的主要靶点有前列腺素-内过氧化物合酶(prostaglandin-endoperoxidase synthase 2,PTGS2)、半胱氨酸天冬氨酸蛋白酶(Caspase-3)、表皮生长因子受体(epidermal growth factor receptor,EGFR)、基质金属蛋白酶9(matrix metalloproteinase-9,MMP9)、MAPKs、TLR4、JUN、STAT3、TLR/NF-κB、PI3 K/Akt、JAK2/STAT3和Nrf2/血红素加氧酶-1(heme oxygenase-1,HO-1)等,具有抗炎、改善血液流变性、保护血管内皮、抗血小板聚集等药理作用;复方丹参滴丸具有扩张冠脉、减少心肌耗氧、增加冠脉流量、增强心肌收缩等作用,还具备用量小、不良反应少,对胃肠刺激小等优点;冠心宁片治疗CHD的靶点包括核受体共激活因子2(nuclear receptor coactivator 2,NCOA2)、一氧化氮合酶2(nitric oxide synthase 2,NOS2)等,主要调控PI3 K/Akt、白细胞介素-17(interleukin-17,IL-17)、低氧诱导因子-1(hypoxic inducible factor-1,HIF-1)等通路;新加丹参饮具有扩张冠脉、增加血流量、改善微循环等作用;冠心丹参方的主要药理活性在于增加冠脉血流量,降低心肌耗氧,从而改善心肌缺血,提高心功能。
Danshen(Salviae Miltiorrhizae Radix et Rhizoma)and its preparations have been widely used in clinical practice,which have good curative effect on coronary heart disease(CHD).The fat-soluble component tanshinone IIA in Danshen(Salvi-ae Miltiorrhizae Radix et Rhizoma)can play the roles of anti-atherosclerosis,anti-myocardial ischemia,anti-myocardial fibrosis and myocardial hypertrophy inhibition,and it exerts effects through different signal transduction pathways[Toll-like receptor 4/nuclear transcription factor-κB(TLR/NF-κB),mitogen-activated protein kinase(MAPK)/NF-κB,phosphoinositide 3 kinase/protein kinase B(PI3 K/AKT),mammalian target of rapamycin/endothelial nitric oxide synthase(mTOR/eNOS),transforming growth factor-β1(TGF-β1)/Smad2/3,stressac-tivated protein kinase(SAPK)/MAPK,extracellular regulated protein kinases(ERK)/nuclear factor erythroid-2-related factor 2(Nrf2),cystatin C(CYSC)/Wnt].Cryptotanshinone can prevent early coronary atherosclerosis by inhibiting inflammatory mediators.Salvianolic acid A,a water-soluble component,can inhibit myocardial cells apoptosis,reduce inflammation and improve myocardial infarction by regulating PI3 K/Akt,serine/threonine kinase(GSK-3β),c-Jun N-terminal kinase(JNK)and ERK1/2 pathways.Salvianolic acid B can alleviate myocardial injury by inhibiting the expressions of TLR4 and nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)inflammasome.Tanshinol can improve microcirculation,anti-inflammation,anti-oxidation,anti-endothelial injury and anti-platelet aggregation by inhibiting Janus tyrosine protein kinase(JAK)/signal transduction and transcriptional activator(STAT)signaling pathways.The main targets of Danshen(Salviae Miltiorrhizae Radix et Rhizoma)water-soluble preparations include prostaglandin-endoperoxidase synthase 2(PTGS2),cysteine proteinase-3(Caspase-3),epidermal growth factor receptor(EGFR),matrix metalloproteinase-9(MMP9),MAPKs,TLR4,JUN,STAT3,TLR/NF-κB,PI3 K/Akt,JAK2/STAT3 and Nrf2/heme oxygenase-1(HO-1),etc.,which can play the roles of anti-inflammation,hemorrheology and pharmacological improvement(protection of vascular endothelium,anti-platelet aggregation).Compound Danshen Dropping Pill(复方丹参滴丸)can dilate coronary artery,reduce myocardial oxygen consumption,increase coronary artery flow and enhance myocardial contraction,with small dosage,few adverse reactions and mild gastrointestinal irritation.The therapeutic targets of Guanxinning Tablet(冠心宁片)for coronary heart disease include nuclear receptor coactivator 2(NCOA2)and nitric oxide synthase 2(NOS2),etc.,which mainly regulate PI3 K/Akt,interleukin-17(IL-17)and hypoxic inducible factor-1(HIF-1)pathways.Xinjia Danshen Decoction(新加丹参饮)can dilate coronary artery,increase blood flow and improve microcirculation.The main pharmacological activity of Guanxin Danshen Decoction(冠心丹参方)is to increase coronary blood flow and reduce myocardial oxygen consumption,thus improving myocardial ischemia and cardiac function.
作者
杨荣来
王凤荣
YANG Ronglail;WANG Fengrong(The First Clinical College of Liaoning University of Traditional Chinese Medicine,Shenyang 110847,Liaoning,China;Affiliated Hospital of Liaoning University of Traditional Chinese Medicine,Shenyang 110032,Liaoning,China)
出处
《中华中医药学刊》
CAS
北大核心
2024年第11期164-169,共6页
Chinese Archives of Traditional Chinese Medicine
基金
国家自然科学基金项目(81874415)
国家中医药管理局重大疑难疾病中西医临床协作项目(国中医药办医政发〔2018〕3号)
辽宁省中医药临床重点学(专)科服务能力建设项目(LNZYXZK201908)。
关键词
丹参
丹参制剂
冠心病
药理研究
作用机制
研究进展
Danshen(Salviae Miltiorrhizae Radix et Rhizoma)
Danshen(Salviae Miltiorrhizae Radix et Rhizoma)preparation
coronary heart disease
pharmacological research
mechanism of action
research progress
