血小板反应素-1在蛛网膜下腔出血后早期脑损伤中的作用及其机制探索

Subarachnoid hemorrhage (SAH) is a serious life-threatening type of hemorrhagic stroke caused by aneurysm disruption and bleeding into the subarachnoid space surrounding the brain, it elicits a wide range of stress responses in brain tissues and results in brain injury. The term early brain injury (EBI) is a concept to explain pathophysiological changes that occur in brain within 72 hours of SAH, such as blood-brain barrier disruption and acute neuroinflammation. Thrombospondin (TSP)-1 is an important member of TSPs family, it is responsible for receptor-mediated signaling pathway activation under kind of pathological changes, following increasing vessel permeability and inducing inflammatory interaction. Based on preliminary experiment results, we found that neurobehavioral impairments was obviously improved and brain edema was significantly alleviated after 24 hours of SAH by inhibiting the expression of TSP-1 in mice brain, however, the detailed mechanisms are still undefined during post-SAH EBI. In this study, to explore the role of TSP-1 in EBI after SAH, we plan to intervene the expression of TSP-1 in mice brain and investigate the outcome of neurobehavioral function, blood-brain barrier integrity and involved inflammation signaling pathways.

蛛网膜下腔出血(SAH)大部分是由于脑动脉瘤破裂所致的一类严重威胁人类健康的出血性卒中，SAH可引起脑内广泛的应激反应并导致脑损伤。早期脑损伤(EBI)是指SAH后72小时内脑组织中所发生的一系列病理生理性改变，如血脑屏障破坏和急性神经炎症反应。血小板反应素(TSP)-1是基质细胞蛋白家族重要成员之一，在多种不同的病理条件下，TSP-1可以经多种受体的介导激活下游信号通路，从而引起血管通透性增加及炎症反应。预实验研究发现，抑制TSP-1在脑内的表达后可以改善小鼠的神经功能障碍，同时还可减轻脑水肿程度，然而TSP-1在SAH后EBI发生发展过程中的详细机制尚不清楚。本研究拟通过干预TSP-1及其受体在小鼠SAH模型体内的表达，评估小鼠SAH后的神经功能状态、血脑屏障的完整性以及所涉及的相关炎症信号通路改变，阐明TSP-1在SAH后EBI发生发展过程中的作用机制，为干预EBI提供新的靶点。

蛛网膜下腔出血(SAH)可引起脑内广泛的应激反应并导致脑损伤。早期脑损伤(EBI)是指SAH后72小时内脑组织中所发生的一系列病理生理性改变。TSP-1可以经多种受体的介导激活下游信号通路，从而引起炎症反应。本研究通过建立SAH小鼠模型，探索TSP-1在SAH后EBI发生发展过程中的作用机制，为干预EBI提供新的靶点。目前的研究结果表明，抑制SAH后TSP-1的表达可以改善小鼠的神经功能障碍、减轻脑水肿、抑制血脑屏障破坏，其分子机制可能与VEGFR2介导的下游炎症信号通路激活相关，为SAH后早期脑损伤的治疗提供了新靶点。

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