阿托伐他汀钙维持未破裂脑动静脉畸形血管内皮结构稳定的研究

Cerebral arteriovenous malformations (cAVMs) are characterized by the abnormal arterial masses that the cerebral arteries directly connect the cerebral veins. cAVMs is susceptible to rupture and bleeding resulting from the long-term high blood pressure and inflammatory responses. These hemodynamic changes result in the damage of vascular endothelial cells, infiltration of red blood cells, micro-bleeding and inflammatory responses, which in turn aggravates the rupture and bleeding of cAVMs. At present, there is no clinically effective treatment to cure the unruptured cAVMs, including surgical resection, intravascular plugging and radiation therapy. Our previous studies have shown that magnetic resonance magnetic sensitive sequence can be used to detect the "microbleeds" of the unruptured cAVMs. In addition, atorvastatin calcium has been demonstrated to have the properties in the stability of vascular endothelial structure and the regulation of immune inflammatory responses. Based on these evidence, in the present study, we investigate the effects of atorvastatin calcium on the unruptured cAVMs in vivo and in vitro, including the stability of vascular endothelial structure and the regulation of immune inflammatory responses. Our study provides a new strategy for the treatment of the unruptured cAVMs.

脑动静脉畸形(cAVMs)是脑内动静脉直接沟通的异常血管团，畸形团长期受高血流压力的冲击以及炎症反应介导，易导致破裂出血。血流动力学改变可导致畸形团血管内皮结构的破坏，红细胞的渗透而发生微出血，进而引发炎症反应向破裂出血转化。目前，手术切除，血管内拴塞以及放射治疗对于未破裂脑动静脉畸形均未明显获益。因此，对于未破裂脑动静脉畸形尚缺乏有效的治疗方式。本课题组拟在以往工作基础上，可利用磁共振磁敏感序列检测出未破裂脑动静脉畸形“微出血”的特点，根据目前阿托伐他汀钙对于稳定血管内皮结构以及调节免疫炎症反应的作用，在动静脉畸形小鼠模型体内以及体外进行阿托伐他汀钙干预，分析动静脉畸形血管内皮细胞结构以及巨噬细胞的表型和炎症因子，探讨阿托伐他汀钙稳定未破裂脑动静脉畸形血管内皮结构以及调节免疫炎症反应的作用，为未破裂脑动静脉畸形的药物治疗提供新的策略。

脑动静脉畸形(cAVMs)是脑内动静脉直接沟通的异常血管团，畸形团长期受高血流压力的冲击以及炎症反应介导，易导致破裂出血。血流动力学改变可导致畸形团血管内皮结构的破坏，红细胞的渗透而发生微出血，进而引发炎症反应向破裂出血转化。目前，手术切除，血管内栓塞以及放射治疗对于未破裂脑动静脉畸形均未明显获益。因此，对于未破裂脑动静脉畸形尚缺乏有效的治疗方式。本课题组拟在以往工作基础上，可利用磁共振磁敏感序列检测出未破裂脑动静脉畸形“微出血”的特点，根据目前阿托伐他汀钙对于稳定血管内皮结构以及调节免疫炎症反应的作用，在动静脉畸形小鼠模型体内以及体外进行阿托伐他汀钙干预，分析动静脉畸形血管内皮细胞结构以及巨噬细胞的表型和炎症因子，探讨阿托伐他汀钙稳定未破裂脑动静脉畸形血管内皮结构以及调节免疫炎症反应的作用，为未破裂脑动静脉畸形的药物治疗提供新的策略。