Botch/Notch1通路在间充质干细胞对动脉瘤性蛛网膜下腔出血后脑微循环的调控机制研究

动脉瘤性蛛网膜下腔（SAH）出血患者死亡率高达40%. SAH后炎症和氧化应激反应造成的脑组织微循环障碍是导致患者死亡的重要原因。我们前期研究证明，MSCs通过分泌Botch来抑制Notch1通路介导的炎症反应，从而减轻SAH后早期的脑损伤。进一步研究发现MSCs可以减轻SAH后的血管痉挛程度，因炎症和氧化应激反应可加剧SAH后的微血管痉挛，我们推测MSCs可能通过分泌Botch来抑制SAH后Notch1通路介导的炎症和氧化应激反应，从而减轻微血管痉挛。本项目拟用颈动脉穿刺法造大鼠SAH模型，静脉注射上调和下调Botch基因的MSCs，再联合阻断和激活Notch1通路，探索MSCs是否通过分泌Botch来抑制SAH后Notch1通路介导的炎症和氧化应激反应，减轻微血管痉挛。本研究通过体内、外实验来探索MSCs减轻SAH后微血管痉挛所致脑损伤的分子机制，为治疗SAH后脑损伤提供新的理论依据

The mortality rate of patients with aneurysmal subarachnoid (SAH) hemorrhage is as high as 40%. Brain microcirculation disturbance caused by inflammation and oxidative stress after SAH is an important cause of death. Our previous studies have demonstrated that MSCs inhibit the Notch1 pathway-mediated inflammatory response by secreting Botch, thereby reducing early brain damage after SAH. Further studies have found that MSCs can reduce the degree of vasospasm after SAH, and inflammation and oxidative stress can aggravate microvascular spasm after SAH. We speculate that MSCs may inhibit Notch1 pathway-mediated inflammation and oxidative stress after SAH by secreting Botch , thereby reducing microvascular spasm. In this study, the rat SAH model was established by carotid artery puncture. The MSCs ,up-regulating and down-regulating the Botch gene, combined with blocking and activating the Notch1 pathway to explore Whether MSCs secreted Botch to inhibit the Notch1 pathway-mediated inflammation and oxidation stress response after SAH, reducing microvascular spasm. This study explores the molecular mechanism of MSCs to alleviate brain damage caused by microvascular spasm after SAH through in vitro and in vivo experiments, and provides a new theoretical basis for the treatment of brain injury after SAH.