Direct thrombin inhibitor argatroban reduces stroke damage in 2 different models.
Direct thrombin inhibitor argatroban reduces stroke damage in 2 different models.
复制标题
DOI：
10.1161/strokeaha.113.004488
复制
发表时间：
2014-03
期刊：
影响因子：
8.3
通讯作者：
Rajput P
中科院分区：
文献类型：
--
作者：
Lyden P;Pereira B;Chen B;Zhao L;Lamb J;Lei IF;Rajput P
我们之前已证明凝血酶抑制剂阿加曲班具有强大的神经保护作用，现在寻求对其神经保护潜力的更多支持。
我们采用行为学和组织学指标；对研究组进行严格设盲；将治疗时间窗延长至缺血发生后3小时；并使用了2种不同的模型。首先，对64只雄性斯普拉格 - 道利大鼠进行2小时大脑中动脉闭塞（MCAo），随后进行学习和记忆测试以及定量组织形态测量。随机分配的治疗药物为0.45mg阿加曲班、生理盐水或0.4U凝血酶。其次，我们在2小时大脑中动脉闭塞后使用量子生物测定法（n = 272）来检测治疗失败的最长延迟时间。
与生理盐水或凝血酶相比，阿加曲班能有力且显著地逆转局灶性缺血导致的学习和记忆缺陷（方差分析，p < 0.03）。当立即给药或延迟1、2、3小时给药时，阿加曲班具有显著的保护作用（采用Bonferroni校正的t检验，p < 0.05），但延迟4小时给药则无保护作用。
我们通过在实际治疗时间窗内进行行为学和组织学测量，获得了阿加曲班对神经血管单元具有保护作用的支持性证据。
We showed previously robust neuroprotection with the thrombin inhibitor argatroban, and now sought additional support for its neuroprotective potential. We used behavioral and histological endpoints; rigorously blinded the study groups; extended the treatment window to 3 hours following ischemia onset; and used 2 separate models. First, 2-h filament MCAo in 64 male Sprague-Dawley rats was followed by learning and memory testing and quantitative histomporphometry. Randomly assigned treatment was 0.45mg argatroban, saline, or 0.4U thrombin. Second, we used the quantal bioassay (n=272) after 2-hour MCAo to detect the longest time delay after which therapy failed. Argatroban powerfully and significantly reversed learning and memory deficits due to focal ischemia compared to saline or thrombin (p<0.03, ANOVA). Argatroban was significantly (p<0.05, t-test with Bonferroni) protective when given immediately or after 1, 2, 3 but not 4 hours delay. We obtained supportive evidence for argatroban protection of the neurovascular unit using behavioral and histological measurements at realistic therapeutic time windows.