以脂氧素A4为中心的信号通路经血管炎症途径参与SAH后脑血流自动调节的机制研究

Patients with subarachnoid hemorrhage(SAH) are often associated with cerebral autoregulation;there may be potential pathophysiological mechanisms. It has been reported that cerebral autoregulation(CA) is compromised in SAH, which leads to the decrease of cerebral blood flow. The intact endothelial cell is important to CA. Neutrophil is involved in pathological process of cerebralvascular inflammation after SAH,and there is neutrophil-endothelial interaction which leads to endothlial injury. In our previous, we found lipoxin A4(LXA4) had lower expression after SAH, which plays anti-inflammation role, but the role of LXA4 in cerebrovascular inflammation is still unknown. We have found mmp-9 expression is concurrent with apoptosis of endothelial cell after SAH. In this research, we will choose SAH rat model to further determine the role of LXA4 in cerebrovascular inflammation. We will assess the relationship between neutrophil and endothelial cell function and CA by using dynamic examination and then confirm the role of 5-LOX/LXA4/ALX pathway in CA dysregulation in cerebrovascular inflammation after SAH. This study analyzes the special pathophysiological changes of cerebrovascular in SAH, which can help to treat it better.

蛛网膜下腔出血（SAH）患者常伴有脑血流自动调节（CA）功能异常,而且CA受损是导致迟发性脑缺血的根本原因，但其作用机制不明。血管内皮细胞功能完整是CA正常的前提。SAH后血管组织发生炎症反应，聚集的中性粒细胞与血管内皮细胞发生相互作用，可以导致内皮细胞损伤。我们前期研究发现脂氧素A4（LXA4）能够抑制SAH后脑组织内中性粒细胞浸润，有抗炎作用，但其在血管炎症中的作用亟待阐明；同时MMP-9与SAH后脑血管内皮细胞凋亡有关。前期研究提示LXA4可能通过MMP-9相关炎症通路对内皮细胞产生影响。本研究将构建SAH大鼠模型，从SAH后血管炎症导致脑血管内皮细胞损伤入手，借助近红外光谱分析仪记录脑氧合状况以反应脑血流自动调节的变化；首先观察血管炎症与脑血流调节的关系，再通过对LXA4及其通路5-LOX/LXA4/ALX的研究，探讨CA受损的血管炎症机制，并验证LXA4对SAH的治疗作用。

蛛网膜下腔出血(SAH)患者常伴有脑血流自动调节(CA)功能异常,而且CA受损是导致迟发性脑缺血的根本原因。血管内皮细胞功能完整是CA正常的前提。SAH后血管组织发生炎症反应，聚集的中性粒细胞与血管内皮细胞发生相互作用，可以导致内皮细胞损伤。本研究通过构建SAH大鼠模型，从SAH后血管炎症导致脑血管内皮细胞损伤入手，借助近红外光谱分析仪记录脑氧合状况以反应脑血流自动调节的变化;首先观察血管炎症与脑血流调节的关系，再通过对LXA4及其通路5-LOX/LXA4/ALX的研究，探讨CA受损的血管炎症机制，并验证LXA4对SAH的治疗作用。研究结果发现SAH后早期即出现脑血流自动调节功能失调，并与SAH大鼠血管炎症反应及内皮细胞受损程度密切相关。LXA4在SAH后EBI发生机制中的作用，为SAH的防治提供新的分子靶点或新的思路。研究发现LXA4通过5-LOX/LXA4/ALX通路经NF-κB/MMP-9途径调控SAH后的血管炎症反应，并参与脑血流自动调节功能。为改善SAH患者预后提供了新的思路。相关研究成果发表SCI论文6篇，1篇已接收待发表。