纤溶酶依赖性调节血脑屏障：tPA 诱导溶栓时的主要考虑因素？
Plasmin-dependent modulation of the blood-brain barrier: a major consideration during tPA-induced thrombolysis?
机构信息
Australian Centre for Blood Diseases, Monash University, Melbourne, Victoria, Australia.
出版信息
J Cereb Blood Flow Metab. 2014 Aug;34(8):1283-96. doi: 10.1038/jcbfm.2014.99. Epub 2014 Jun 4.
Abstract
Plasmin, the principal downstream product of tissue-type plasminogen activator (tPA), is known for its potent fibrin-degrading capacity but is also recognized for many non-fibrinolytic activities. Curiously, plasmin has not been conclusively linked to blood-brain barrier (BBB) disruption during recombinant tPA (rtPA)-induced thrombolysis in ischemic stroke. This is surprising given the substantial involvement of tPA in the modulation of BBB permeability and the co-existence of tPA and plasminogen in both blood and brain throughout the ischemic event. Here, we review the work that argues a role for plasmin together with endogenous tPA or rtPA in BBB alteration, presenting the overall controversy around the topic yet creating a rational case for an involvement of plasmin in this process.
摘要
纤溶酶是组织型纤溶酶原激活物（tPA）的主要下游产物，以其强大的纤维蛋白降解能力而闻名，但也具有许多非纤维蛋白溶解活性。奇怪的是，纤溶酶与缺血性中风中重组 tPA（rtPA）诱导的溶栓过程中血脑屏障（BBB）的破坏并没有明确的联系。鉴于 tPA 大量参与 BBB 通透性的调节，以及 tPA 和纤溶酶原在整个缺血事件中同时存在于血液和大脑中，这令人惊讶。在这里，我们回顾了认为纤溶酶与内源性 tPA 或 rtPA 一起在 BBB 改变中起作用的工作，提出了围绕该主题的总体争议，但为纤溶酶在该过程中的参与提供了合理的依据。
相似文献
1
Plasmin-dependent modulation of the blood-brain barrier: a major consideration during tPA-induced thrombolysis?纤溶酶依赖性调节血脑屏障：tPA 诱导溶栓时的主要考虑因素？
J Cereb Blood Flow Metab. 2014 Aug;34(8):1283-96. doi: 10.1038/jcbfm.2014.99. Epub 2014 Jun 4.
2
Microglial-mediated PDGF-CC activation increases cerebrovascular permeability during ischemic stroke.小胶质细胞介导的血小板衍生生长因子-CC 激活增加缺血性脑卒中期间的脑血管通透性。
Acta Neuropathol. 2017 Oct;134(4):585-604. doi: 10.1007/s00401-017-1749-z. Epub 2017 Jul 19.
3
Recombinant ADAMTS13 reduces tissue plasminogen activator-induced hemorrhage after stroke in mice.重组 ADAMTS13 可减少小鼠中风后组织型纤溶酶原激活物诱导的出血。
Ann Neurol. 2013 Feb;73(2):189-98. doi: 10.1002/ana.23762. Epub 2012 Dec 31.
4
Normobaric hyperoxia reduces the neurovascular complications associated with delayed tissue plasminogen activator treatment in a rat model of focal cerebral ischemia.常压高氧可减少局灶性脑缺血大鼠模型中与组织型纤溶酶原激活剂延迟治疗相关的神经血管并发症。
Stroke. 2009 Jul;40(7):2526-31. doi: 10.1161/STROKEAHA.108.545483. Epub 2009 May 28.
5
Remote ischemic conditioning attenuates blood-brain barrier disruption after recombinant tissue plasminogen activator treatment via reducing PDGF-CC.远程缺血预处理通过减少 PDGF-CC 减轻重组组织型纤溶酶原激活剂治疗后血脑屏障的破坏。
Pharmacol Res. 2023 Jan;187:106641. doi: 10.1016/j.phrs.2022.106641. Epub 2022 Dec 29.
6
Phosphorylated recombinant HSP27 protects the brain and attenuates blood-brain barrier disruption following stroke in mice receiving intravenous tissue-plasminogen activator.磷酸化重组 HSP27 可保护大脑，并减轻接受静脉注射组织型纤溶酶原激活物的中风小鼠血脑屏障的破坏。
PLoS One. 2018 May 24;13(5):e0198039. doi: 10.1371/journal.pone.0198039. eCollection 2018.
7
Progesterone attenuates hemorrhagic transformation after delayed tPA treatment in an experimental model of stroke in rats: involvement of the VEGF-MMP pathway.孕激素可减轻大鼠实验性卒中模型中 tPA 延迟治疗后的出血性转化：涉及 VEGF-MMP 通路。
J Cereb Blood Flow Metab. 2014 Jan;34(1):72-80. doi: 10.1038/jcbfm.2013.163. Epub 2013 Sep 18.
8
Comparison of plasmin with recombinant tissue-type plasminogen activator in lysis of cerebral thromboemboli retrieved from patients with acute ischemic stroke.比较纤溶酶与重组组织型纤溶酶原激活剂在急性缺血性脑卒中患者脑血栓栓子溶解中的作用。
Stroke. 2011 Aug;42(8):2222-8. doi: 10.1161/STROKEAHA.110.609198. Epub 2011 Jun 23.
9
Mesenchymal stem cell-derived extracellular vesicles attenuate tPA-induced blood-brain barrier disruption in murine ischemic stroke models.间充质干细胞衍生的细胞外囊泡可减轻小鼠缺血性中风模型中组织型纤溶酶原激活剂诱导的血脑屏障破坏。
Acta Biomater. 2022 Dec;154:424-442. doi: 10.1016/j.actbio.2022.10.022. Epub 2022 Oct 29.
10
High-density lipoprotein-based therapy reduces the hemorrhagic complications associated with tissue plasminogen activator treatment in experimental stroke.基于高密度脂蛋白的治疗可减少组织型纤溶酶原激活物治疗实验性中风相关的出血并发症。
Stroke. 2013 Mar;44(3):699-707. doi: 10.1161/STROKEAHA.112.667832. Epub 2013 Feb 19.
引用本文的文献
1
Micrometer-scale tPA beads amplify plasmin generation for enhanced thrombolytic therapy.微米级组织型纤溶酶原激活剂（tPA）微珠可增强纤溶酶生成，用于强化溶栓治疗。
Bioeng Transl Med. 2025 Mar 3;10(4):e70012. doi: 10.1002/btm2.70012. eCollection 2025 Jul.
2
Shared interactions of six neurotropic viruses with 38 human proteins: a computational and literature-based exploration of viral interactions and hijacking of human proteins in neuropsychiatric disorders.六种嗜神经病毒与38种人类蛋白质的共享相互作用：基于计算和文献的神经精神疾病中病毒相互作用及对人类蛋白质劫持的探索
Discov Ment Health. 2025 Feb 22;5(1):18. doi: 10.1007/s44192-025-00128-2.
3
Role of Nanotechnology in Ischemic Stroke: Advancements in Targeted Therapies and Diagnostics for Enhanced Clinical Outcomes.纳米技术在缺血性中风中的作用：靶向治疗与诊断的进展以改善临床结局
J Funct Biomater. 2025 Jan 1;16(1):8. doi: 10.3390/jfb16010008.
4
Harnessing micrometer-scale tPA beads for high plasmin generation and accelerated fibrinolysis.利用微米级组织型纤溶酶原激活剂（tPA）微珠实现高纤溶酶生成和加速纤维蛋白溶解。
bioRxiv. 2024 Nov 8:2024.11.06.621942. doi: 10.1101/2024.11.06.621942.
5
Recombinant tissue plasminogen activator protects neurons after intracerebral hemorrhage through activating the PI3K/AKT/mTOR pathway.重组组织型纤溶酶原激活剂通过激活PI3K/AKT/mTOR通路在脑出血后保护神经元。
Neural Regen Res. 2024 Jul 29. doi: 10.4103/NRR.NRR-D-23-01953.
6
Tranexamic acid for haemostasis and beyond: does dose matter?氨甲环酸用于止血及其他方面：剂量重要吗？
Thromb J. 2023 Sep 12;21(1):94. doi: 10.1186/s12959-023-00540-0.
7
Tranexamic acid in a mouse model of cerebral amyloid angiopathy: setting the stage for a novel stroke treatment approach.氨甲环酸在脑淀粉样血管病小鼠模型中的应用：为新型中风治疗方法奠定基础。
Res Pract Thromb Haemost. 2023 Aug 9;7(6):102166. doi: 10.1016/j.rpth.2023.102166. eCollection 2023 Aug.
8
A Scoping Review on Biomarkers of Endothelial Dysfunction in Small Vessel Disease: Molecular Insights from Human Studies.小血管疾病内皮功能障碍生物标志物的范围综述：来自人类研究的分子见解。
Int J Mol Sci. 2023 Aug 23;24(17):13114. doi: 10.3390/ijms241713114.
9
Platelet-targeted thrombolysis for treatment of acute ischemic stroke.血小板靶向溶栓治疗急性缺血性脑卒中。
Blood Adv. 2023 Feb 28;7(4):561-574. doi: 10.1182/bloodadvances.2021006691.
10
QiShenYiQi Inhibits Tissue Plasminogen Activator-Induced Brain Edema and Hemorrhage after Ischemic Stroke in Mice.芪参益气抑制组织型纤溶酶原激活剂诱导的小鼠缺血性中风后脑水肿和出血。
Front Pharmacol. 2022 Jan 12;12:759027. doi: 10.3389/fphar.2021.759027. eCollection 2021.
本文引用的文献
1
Improved method for the preparation of a human cell-based, contact model of the blood-brain barrier.用于制备基于人细胞的血脑屏障接触模型的改进方法。
J Vis Exp. 2013 Nov 12(81):e50934. doi: 10.3791/50934.
2
Tissue-type plasminogen activator is not necessary for platelet-derived growth factor-c activation.组织型纤溶酶原激活剂对于血小板衍生生长因子-C的激活并非必需。
Biochim Biophys Acta. 2014 Feb;1842(2):318-25. doi: 10.1016/j.bbadis.2013.11.013. Epub 2013 Nov 19.
3
Optical imaging to map blood-brain barrier leakage.用于绘制血脑屏障渗漏情况的光学成像技术。
Sci Rep. 2013 Nov 1;3:3117. doi: 10.1038/srep03117.
4
Hemostasis and alterations of the central nervous system.止血和中枢神经系统改变。
Semin Thromb Hemost. 2013 Nov;39(8):856-75. doi: 10.1055/s-0033-1357490. Epub 2013 Oct 28.
5
Progesterone attenuates hemorrhagic transformation after delayed tPA treatment in an experimental model of stroke in rats: involvement of the VEGF-MMP pathway.孕激素可减轻大鼠实验性卒中模型中 tPA 延迟治疗后的出血性转化：涉及 VEGF-MMP 通路。
J Cereb Blood Flow Metab. 2014 Jan;34(1):72-80. doi: 10.1038/jcbfm.2013.163. Epub 2013 Sep 18.
6
Prevention of rt-PA induced blood-brain barrier component degradation by the poly(ADP-ribose)polymerase inhibitor PJ34 after ischemic stroke in mice.聚（ADP-核糖）聚合酶抑制剂 PJ34 对缺血性脑卒中后 rt-PA 诱导的血脑屏障成分降解的预防作用。
Exp Neurol. 2013 Oct;248:416-28. doi: 10.1016/j.expneurol.2013.07.007. Epub 2013 Jul 20.
7
Ablation of astrocytic laminin impairs vascular smooth muscle cell function and leads to hemorrhagic stroke.星形胶质细胞层粘连蛋白的消融会损害血管平滑肌细胞的功能，导致出血性中风。
J Cell Biol. 2013 Jul 22;202(2):381-95. doi: 10.1083/jcb.201212032. Epub 2013 Jul 15.
8
Plasminogen receptors: the first quarter century.纤溶酶原受体：第一个四分之一世纪。
Semin Thromb Hemost. 2013 Jun;39(4):329-37. doi: 10.1055/s-0033-1334483. Epub 2013 Mar 26.
9
Plasmin Activation of Glial Cells through Protease-Activated Receptor 1.纤溶酶通过蛋白酶激活受体1激活神经胶质细胞。
Patholog Res Int. 2013;2013:314709. doi: 10.1155/2013/314709. Epub 2013 Jan 28.
10
Nucleocytoplasmic coagulation: an injury-induced aggregation event that disulfide crosslinks proteins and facilitates their removal by plasmin.核质凝聚：一种损伤诱导的聚集事件，通过二硫键交联蛋白质并促进其被纤溶酶清除。
Cell Rep. 2012 Oct 25;2(4):889-901. doi: 10.1016/j.celrep.2012.08.026. Epub 2012 Oct 4.
Zotero 插件