EphA4-Fc在小鼠脑中动脉局灶缺血中神经保护作用的研究

EphA4参与调节脑缺血/再灌注后的损伤，之前并未有研究说明其作用机制。在本研究中，我们发现EphA4-Fc可以竞争性抑制EphA4，在大脑中动脉缺血（MCAO）小鼠模型中具有显著的神经保护作用。小鼠MCAO手术之前或之后接受EphA4-Fc治疗，可在24或72小时后显著减少约10%的缺血性脑水肿。与此同时，脑梗塞面积也减少了10-30%，而且神经评分也得到了明显的改善。我们的结果表明，EphA4-Fc治疗后导致内皮细胞通透性的变化和脑水肿的减少。我们使用了原代血管内皮细胞进行了体外实验，结果表明EphA4-Fc抑制了应力纤维的形成，并在缺氧-葡萄糖剥夺和再灌注治疗期间保持紧密连接的完整性。上述结果表明，抑制EphA4的激活在维持内皮细胞膜形态完整性方面起着关键作用，EphA4-Fc是EphA4介导的内皮细胞功能丧失的有效阻断剂，并且EphA4-Fc的治疗可以有效降低脑缺血后水肿和脑梗塞的程度。由于EphA4-Fc最近在人类I期试验中表现出良好的耐受性，本研究的结果表明，它在人类中风的治疗应用中具有潜力。EphA4参与调节脑缺血/再灌注后的损伤，之前并未有研究说明其作用机制。在本研究中，我们发现EphA4-Fc可以竞争性抑制EphA4，在大脑中动脉缺血（MCAO）小鼠模型中具有显著的神经保护作用。小鼠MCAO手术之前或之后接受EphA4-Fc治疗，可在24或72小时后显著减少约10%的缺血性脑水肿。与此同时，脑梗塞面积也减少了10-30%，而且神经评分也得到了明显的改善。我们的结果表明，EphA4-Fc治疗后导致内皮细胞通透性的变化和脑水肿的减少。我们使用了原代血管内皮细胞进行了体外实验，结果表明EphA4-Fc抑制了应力纤维的形成，并在缺氧-葡萄糖剥夺和再灌注治疗期间保持紧密连接的完整性。上述结果表明，抑制EphA4的激活在维持内皮细胞膜形态完整性方面起着关键作用，EphA4-Fc是EphA4介导的内皮细胞功能丧失的有效阻断剂，并且EphA4-Fc的治疗可以有效降低脑缺血后水肿和脑梗塞的程度。由于EphA4-Fc最近在人类I期试验中表现出良好的耐受性，本研究的结果表明，它在人类中风的治疗应用中具有潜力。

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