Human recombinant tissue-plasminogen activator (alteplase): why not use the 'human' dose for stroke studies in rats?

Human recombinant tissue-plasminogen activator (alteplase): why not use the 'human' dose for stroke studies in rats?
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DOI:
10.1038/jcbfm.2010.33
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发表时间:
2010-05-01
影响因子:
6.3
通讯作者:
Abraini, Jacques H.
Abraini, Jacques H.
中科院分区:
医学1区
文献类型:
--
作者:
Haelewyn, Benoit;Risso, Jean-Jacques;Abraini, Jacques H.

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由于一项开创性的工作表明,在体外大鼠的纤溶系统对重组组织纤溶酶原激活剂(RtPA)的敏感性比人类系统低10倍,因此大多数临床前研究都是使用10 mg/kg rtPA(中风患者的临床剂量)。在这项研究中,我们比较了这些剂量对血栓栓塞性卒中大鼠平均再通时间、再通斜率、脑梗塞体积和水肿的影响。我们的数据表明,对于啮齿类动物的临床前卒中研究,0.9 mg/kg的rtPA剂量与10 mg/kg的剂量一样合适。《脑血流与代谢杂志》(2010年)30900903DOI:10.1038/jcbfm.2010.33;2010年3月10日在线出版
Since a pioneer work that has shown in vitro that the rat's fibrinolytic system is 10-fold less sensitive to recombinant tissue-plasminogen activator (rtPA) than the human system, most preclinical studies are performed with 10 instead of 0.9 mg/kg rtPA (the clinical dose in stroke patients). In this study, we compared the effects of these doses on mean time to reperfusion, reperfusion slope, brain infarct volume and edema in a rat model of thrombo-embolic stroke. Our data provide evidence that the dose of 0.9 mg/kg rtPA is as appropriate as that of 10 mg/kg for preclinical stroke studies in rodents. Journal of Cerebral Blood Flow & Metabolism (2010) 30, 900-903; doi: 10.1038/jcbfm.2010.33; published online 10 March 2010