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1.陆军军医大学第二附属医院神经内科,重庆 400037
2.重庆脑与智能科学中心广阳湾实验室,重庆 400064
主治医师,博士研究生。研究方向:急性脑血管防治基础与临床转化研究。电话:023-68763212。E-mail:kongweilin96@ whu.edu.cn
主任医师,教授,博士生导师,博士。研究方向:急性脑血管病发生机制及防治的基础与临床转化研究。电话:023-68755613。E-mail:yangqwmlys@163.com
纸质出版日期:2023-02-28,
收稿日期:2022-11-08,
修回日期:2023-01-01,
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孔维麟,杨清武.急性缺血性卒中溶栓药物的研究进展 Δ[J].中国药房,2023,34(04):497-501.
KONG Weilin,YANG Qingwu.Research progress of thrombolytic drugs for acute ischemic stroke[J].ZHONGGUO YAOFANG,2023,34(04):497-501.
孔维麟,杨清武.急性缺血性卒中溶栓药物的研究进展 Δ[J].中国药房,2023,34(04):497-501. DOI: 10.6039/j.issn.1001-0408.2023.04.22.
KONG Weilin,YANG Qingwu.Research progress of thrombolytic drugs for acute ischemic stroke[J].ZHONGGUO YAOFANG,2023,34(04):497-501. DOI: 10.6039/j.issn.1001-0408.2023.04.22.
急性缺血性卒中是一种发病率、致死率、致残率、复发率均较高的脑血管疾病,严重危害患者的健康。溶栓药物通过激活纤维蛋白溶酶原(简称“纤溶酶原”),来快速溶解血栓,减少血小板聚集,实现血管成功再通,对急性缺血性卒中的治疗具有关键作用。本研究基于当前国内外研究,从溶栓药物的作用原理及分类运用等方面进行综述。结果发现,从不具有纤维蛋白特异性的第一代溶栓药物链激酶,到第三代溶栓药物替奈普酶,第三代溶栓药物既保留了直接活化纤溶酶原的特性,还增强了纤维蛋白特异性,延长了半衰期,有效性和安全性更好。随着研究的发展,具有纤溶酶原激活物抑制作用的小分子化合物,或者改造具有较强体内抗纤溶酶原激活物抑制活性的溶栓药物,或者从微生物、天然植物中寻找新型的具有溶栓作用的小分子物质,成为了新型溶栓药物研究的热点。新型溶栓药物可能因具有更强的溶栓效率和更少的副作用,而成为当前溶栓治疗的替代药物。
Acute ischemic stroke is a cerebrovascular disease with high incidence, high mortality and disability, and high recurrence rate, which seriously endangers patients’ health. Thrombolytic drugs play a key role in the treatment of acute ischemic stroke by activating plasminogen, rapidly dissolving thrombi, reducing platelet aggregation, and achieving successful recanalization. In this study, we reviewed the principle of action of thrombolytic drugs, their classification and use on the basis of current research progress at home and abroad. The results show that the safety and efficacy of thrombolytic drugs have improved significantly from the first generation of thrombolytic drugs, streptokinase, which is not fibrin-specific, to the third generation of thrombolytic drugs, tenecteplase, which not only retain the characteristics of directly activating plasminogen, but also enhance the specificity of fibrin and prolong the half-life. With the development of research, small-molecular compounds with the inhibition of plasminogen activator, or the modification of thrombolytic drugs with strong anti-plasminogen activator inhibition activity
in vivo
, or the search for new small-molecular substances with thrombolytic effect from microorganisms and natural plants, have become the focus of research on new thrombolytic drugs. The new thrombolytic drugs are likely to replace the current thrombolytic drugs because of greater thrombolytic efficacy and fewer side effects.
急性缺血性卒中溶栓药物纤溶酶原激活物
acute ischemic strokethrombolytic drugplasminogen activator
王拥军,李子孝,谷鸿秋,等. 中国卒中报告2020:中文版:1[J]. 中国卒中杂志,2022,17(5):433-447.
POWERS W J,RABINSTEIN A A,ACKERSON T,et al. 2018 guidelines for the early management of patients with acute ischemic stroke:a guideline for healthcare professionals from the American Heart Association/American Stroke Association[J]. Stroke,2018,49(3):e46-e110.
ZERNA C,THOMALLA G,CAMPBELL B C V,et al. Current practice and future directions in the diagnosis and acute treatment of ischaemic stroke[J]. Lancet,2018,392(10154):1247-1256.
ESMON C T. Basic mechanisms and pathogenesis of venous thrombosis[J]. Blood Rev,2009,23(5):225-229.
CASTELLINO F J,PLOPLIS V A. Structure and function of the plasminogen/plasmin system[J]. Thromb Haemost,2005,93(4):647-654.
KIRMANI J F,ALKAWI A,PANEZAI S,et al. Advances in thrombolytics for treatment of acute ischemic stroke[J]. Neurology,2012,79(13 Suppl 1):S119-S125.
许燕艳,陈珊莉,陈丹,等. 缺血性脑卒中溶栓药物研究进展[J]. 生物工程学报,2020,36(10):2029-2039.
ADIVITIYA,KHASA Y P. The evolution of recombinant thrombolytics:current status and future directions[J]. Bioengineered,2017,8(4):331-358.
TILLETT W S,GARNER R L. The fibrinolytic activity of hemolytic streptococci[J]. J Exp Med,1933,58(4):485-502.
CLIFFTON E E. The use of plasmin in humans[J]. Ann N Y Acad Sci,1957,68(1):209-229.
BANERJEE A,CHISTI Y,BANERJEE U C. Streptokinase:a clinically useful thrombolytic agent[J]. Biotechnol Adv,2004,22(4):287-307.
MACFARLANE R G,PILLING J. Fibrinolytic activity of normal urine[J]. Nature,1947,159(4049):779.
MCNAMARA T O,FISCHER J R. Thrombolysis of peripheral arterial and graft occlusions:improved results using high-dose urokinase[J]. Am J Roentgenol,1985,144(4):769-775.
中华医学会神经病学分会,中华医学会神经病学分会脑血管病学组,彭斌,等. 中国急性缺血性脑卒中诊治指南2018[J]. 中华神经科杂志,2018,51(9):666-682.
RIJKEN D C,COLLEN D. Purification and characterization of the plasminogen activator secreted by human melanoma cells in culture[J]. J Biol Chem,1981,256(13):7035-7041.
The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. Tissue plasminogen activator for acute ischemic stroke[J]. N Engl J Med,1995,333(24):1581-1587.
BROTT T. Thrombolysis for stroke[J]. Arch Neurol,1996,53(12):1305-1306.
HACKE W,KASTE M,BLUHMKI E,et al. Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke[J]. N Engl J Med,2008,359(13):1317-1329.
IST-Collaborative Group,SANDERCOCK P,WARDLAW J M,et al. The benefits and harms of intravenous thrombolysis with recombinant tissue plasminogen activator within 6 h of acute ischaemic stroke(the third international stroke trial[IST-3]):a randomised controlled trial[J]. Lancet,2012,379(9834):2352-2363.
MA H,CAMPBELL B C V,PARSONS M W,et al. Thrombolysis guided by perfusion imaging up to 9 hours after onset of stroke[J]. N Engl J Med,2019,380(19):1795-1803.
CHEN J,LI H F,LEI H H,et al. Determinants for a low dose of alteplase and its relationship to a lower intracerebral bleeding risk in acute ischemic stroke[J]. Int J Med Sci,2022,19(12):1762-1769.
YAMAGUCHI T,MORI E,MINEMATSU K,et al. Alteplase at 0.6 mg/kg for acute ischemic stroke within 3 hours of onset:Japan Alteplase Clinical Trial(J-ACT)[J]. Stroke,2006,37(7):1810-1815.
MORI E,MINEMATSU K,NAKAGAWARA J,et al. Effects of 0.6 mg/kg intravenous alteplase on vascular and clinical outcomes in middle cerebral artery occlusion:Japan Alteplase Clinical Trial Ⅱ(J-ACT Ⅱ)[J]. Stroke,2010,41(3):461-465.
NAKAGAWARA J,MINEMATSU K,OKADA Y,et al. Thrombolysis with 0.6 mg/kg intravenous alteplase for acute ischemic stroke in routine clinical practice:the Japan post-Marketing Alteplase Registration Study(J-MARS)[J]. Stroke,2010,41(9):1984-1989.
TOYODA K,KOGA M,IGUCHI Y,et al. Guidelines for intravenous thrombolysis(recombinant tissue-type plasminogen activator),the third edition,March 2019:a guideline from the Japan Stroke Society[J]. Neurol Med Chir(Tokyo),2019,59(12):449-491.
ANDERSON C S,ROBINSON T,LINDLEY R I,et al. Low-dose versus standard-dose intravenous alteplase in acute ischemic stroke[J]. N Engl J Med,2016,374(24):2313-2323.
LIU M Y,PAN Y S,ZHOU L C,et al. Low-dose rt-PA may not decrease the incidence of symptomatic intracranial haemorrhage in patients with high risk of sympto-matic intracranial haemorrhage[J]. Neurol Res,2019,41(5):473-479.
CHAO A C,LIU C K,CHEN C H,et al. Different doses of recombinant tissue-type plasminogen activator for acute stroke in Chinese patients[J]. Stroke,2014,45(8):2359-2365.
NORDT T K,BODE C. Thrombolysis:newer thrombolytic agents and their role in clinical medicine[J]. Heart,2003,89(11):1358-1362.
PARSONS M,SPRATT N,BIVARD A,et al. A rando-mized trial of tenecteplase versus alteplase for acute ische-mic stroke[J]. N Engl J Med,2012,366(12):1099-1107.
HUANG X Y,CHERIPELLI B K,LLOYD S M,et al. Alteplase versus tenecteplase for thrombolysis after ischae-mic stroke(ATTEST):a phase 2,randomised,open-label,blinded endpoint study[J]. Lancet Neurol,2015,14(4):368-376.
LOGALLO N,NOVOTNY V,ASSMUS J,et al. Tenecteplase versus alteplase for management of acute ischaemic stroke(NOR-TEST):a phase 3,randomised,open-label,blinded endpoint trial[J]. Lancet Neurol,2017,16(10):781-788.
CAMPBELL B C V,MITCHELL P J,CHURILOV L,et al. Tenecteplase versus alteplase before thrombectomy for ischemic stroke[J]. N Engl J Med,2018,378(17):1573-1582.
LOGALLO N,KVISTAD C E,THOMASSEN L. Therapeutic potential of tenecteplase in the management of acute ischemic stroke[J]. CNS Drugs,2015,29(10):811-818.
WARACH S J,DULA A N,JrMILLING T J. Tenecteplase thrombolysis for acute ischemic stroke[J]. Stroke,2020,51(11):3440-3451.
PARSONS M W,MITEFF F,BATEMAN G A,et al. Acute ischemic stroke:imaging-guided tenecteplase treatment in an extended time window[J]. Neurology,2009,72(10):915-921.
BIVARD A,ZHAO H,CHURILOV L,et al. Comparison of tenecteplase with alteplase for the early treatment of ischaemic stroke in the Melbourne Mobile Stroke Unit(TASTE-A):a phase 2,randomised,open-label trial[J]. Lancet Neurol,2022,21(6):520-527.
AKHTER M S,BISWAS A,ABDULLAH S M,et al. The role of PAI-1 4G/5G promoter polymorphism and its levels in the development of ischemic stroke in young Indian population[J]. Clin Appl Thromb Hemost,2017,23(8):1071-1076.
LI G H,LIU Y M,LI X H,et al. Association of PAI-1 4G/5G polymorphism with ischemic stroke in Chinese patients with type 2 diabetes mellitus[J]. Genet Test Mol Biomarkers,2018,22(9):554-560.
WU Q Y,ZHAO Z C. Inhibition of PAI-1:a new anti-thrombotic approach[J]. Curr Drug Targets Cardiovasc Haematol Disord,2002,2(1):27-42.
VAUGHAN D E,DE TAEYE B M,EREN M. PAI-1 antagonists:predictable indications and unconventional applications[J]. Curr Drug Targets,2007,8(9):962-970.
PENG S Z,XUE G P,CHEN S L,et al. tPA point mutation at autolysis loop enhances resistance to PAI-1 inhibition and catalytic activity[J]. Thromb Haemost,2019,119(1):77-86.
PENG S Z,XUE G P,GONG L H,et al. A long-acting PAI-1 inhibitor reduces thrombus formation[J]. Thromb Haemost,2017,117(7):1338-1347.
FRIEDERICH P W,LEVI M,BIEMOND B J,et al. Novel low-molecular-weight inhibitor of PAI-1(XR5118)promotes endogenous fibrinolysis and reduces postthrombolysis thrombus growth in rabbits[J]. Circulation,1997,96(3):916-921.
韩廷廷. 纤溶酶原激活物抑制剂1(PAI-1)天然小分子抑制剂的筛选和分子药理活性研究[D]. 大连:辽宁师范大学,2016.
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