Effects of tissue plasminogen activator and annexin A2 combination therapy on long-term neurological outcomes of rat focal embolic stroke.
Effects of tissue plasminogen activator and annexin A2 combination therapy on long-term neurological outcomes of rat focal embolic stroke.
复制标题
组织纤溶酶原激活剂和膜联蛋白A2联合疗法对大鼠局灶性栓塞性中风的长期神经系统结局的影响。
DOI：
10.1161/strokeaha.113.003823
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发表时间：
2014-02
期刊：
影响因子：
8.3
通讯作者：
Wang X
中科院分区：
文献类型：
--
作者：
Wang X;Fan X;Yu Z;Liao Z;Zhao J;Mandeville E;Guo S;Lo EH;Wang X
已知组织型纤溶酶原激活剂（tPA）与重组膜联蛋白A2（rA 2）组合可减少局灶性缺血后的急性脑损伤。在这里，我们想知道tPA和rA 2联合治疗是否也能带来持续的长期神经功能改善。我们在大鼠局灶性栓塞性脑缺血模型中比较了单独静脉注射高剂量tPA（10 mg/kg）与低剂量tPA（5 mg/kg）+10 mg/kg rA 2的组合的作用。所有大鼠在栓塞后3小时进行处理。在1个月时评估脑组织和神经系统结局。通过免疫组化分析梗死周围区域内源性神经血管重塑的替代生物标志物。与单独使用高剂量tPA相比，低剂量tPA + rA 2在卒中后1个月显著减少了梗死并改善了神经功能。在梗死周围区域，tPA加rA 2联合治疗也显著增加微血管密度、VEGF和突触素表达。与传统的高剂量tPA单独治疗相比，低剂量tPA联合rA 2治疗可能提供一种安全有效的方法来改善卒中后的长期神经功能结局。
Tissue type plasminogen activator (tPA) in combination with recombinant annexin A2 (rA2) is known to reduce acute brain damage after focal ischemia. Here, we ask whether tPA plus rA2 combination therapy can lead to sustained long term neurological improvements as well. We compared the effects of intravenous high-dose tPA alone (10mg/kg) versus a combination of low-dose tPA (5mg/kg) plus 10 mg/kg rA2 in a model of focal embolic cerebral ischemia in rats. All rats were treated at 3 hours after embolization. Brain tissue and neurological outcomes were assessed at 1 month. Surrogate biomarkers for endogenous neurovascular remodeling in peri-infarct area were analyzed by immunohistochemistry. Compared to high-dose tPA alone, low-dose tPA plus rA2 significantly decreased infarction and improved neurological function at 1 month post-stroke. In peri-infarct areas, tPA-plus-rA2 combination therapy also significantly augmented microvessel density, VEGF and synaptophysin expression. Compared to conventional high-dose tPA alone, combination low-dose tPA plus rA2 therapy may provide a safe and effective way to improve long term neurological outcomes after stroke.