脑水肿是脑梗死的重要并发症，也是脑梗死患者死亡的重要原因。水通道蛋白AQP4表达增加在脑梗死后脑水肿形成中起主要作用，但目前没有AQP4的特异性外源性拮抗剂，因此研究其内源性调控机制具有重要意义。最新研究显示，在非脑梗死性脑水肿模型中，精氨酸加压素（AVP）可以调控AQP4的表达减轻脑水肿，而AVP受体V1拮抗剂有一定抗脑梗死后脑水肿作用，因此，我们推论“AVP通过调控AQP4的表达从而促进犬脑梗死后脑水肿的形成”。我们前期利用介入微创技术建立犬大脑中动脉栓塞模型，证实犬血浆中AVP水平明显升高，而脑梗死周围组织中AQP4的表达亦明显增加。为进一步验证我们的假说，本研究拟在前期研究基础上，通过犬大脑中动脉栓塞模型，结合细胞学、分子生物学和药理学，深入探讨AVP调控AQP4表达在脑梗死后脑水肿形成中的作用，阐明AVP对AQP4表达的调控机制，为临床治疗脑梗死后脑水肿提供有价值的理论依据。

Brain edema is a serious complication of ischemic stroke. Aquaporin-4 (AQP4) plays an important role in the evolution of ischemia-evoked cerebral edema. Since no agents have been shown antagonistic effect to AQP4, a promising focus of relieving brain edema is to modulate the expression of AQP4. Recent studies indicated that the expression of AQP4 was modulated by arginine vasopressin (AVP) through V1 receptor in the evolution of edema after traumatic or intracerebral hemorrhagic brain injury in mice, and demonstrated the anti-edema effects of AVP V1 receptor antagonists in ischemic stroke model. Therefore we suppose that AVP mediates ischemia-evoked cerebral edema through modulating AQP4 expression. In the canine middle cerebral artery occlusion model set up in our preliminary experiments, we found that the plasma level of copeptin (the C-terminal portion of provasopressin) elevated, and the expression of AQP4 increased in the brain tissue at the border of infarct core. Based on our preliminary experiments, the current study aims to investigate the role and mechanism of AVP on AQP4 expression in brain edema formation after cerebral ischemia, and test the effect of attenuating ischemia-evoked cerebral edema of AVP V1receptor antagonist. These results will be helpful for understanding the molecular mechanism of brain edema after cerebral ischemia, and developing new agents to improve clinical outcome of more patients with acute ischemic stroke.