基于外泌体miR-210/HIF-1α/VEGF/VEGFR2信号轴调控NVU重建探讨电针改善慢性脑缺血后学习记忆障碍的机制

学习记忆障碍是慢性脑缺血的核心症状，与神经血管单元（NVU）稳态关系密切。电针百会、神庭穴对其疗效明确，但机制不明。激活HIF-1α/VEGF/VEGFR2信号通路以促进血管新生是维持NVU稳态的重要途径，外泌体miR-210以HIF-1α/VEGF/VEGFR2信号轴为载体调控脑血管新生，故我们提出“外泌体miR-210介导HIF-1α/VEGF/VEGFR2通路参与电针重建NVU稳态”假说。本项目构建慢性脑缺血模型鼠，电针百会、神庭，观察学习记忆改变，fMRI-DTI追踪前额叶-海马白质神经纤维束变化，激光共聚焦观察神经元、小胶质细胞、星型胶质细胞改变，免疫组化观察微血管密度变化，Western blot检测HIF-1α、VEGF、VEGFR2、APQ4、ZO-1蛋白变化，透射电镜观察外泌体形态改变，qRT-PCR检测miR-210水平，尝试揭示电针改善慢性脑缺血致学习记忆障碍的机制。

Learning and memory impairment is the core symptom of chronic cerebral ischemia, which is closely related to the (NVU) homeostasis of neurovascular units. Electroacupuncture at Baihui and Shenting points has a clear curative effect, but the mechanism is not clear. Activating HIF-1 α / VEGF/VEGFR2 signal pathway to promote angiogenesis is an important way to maintain NVU homeostasis. Exosome miR-210 uses HIF-1 α / VEGF/VEGFR2 signal axis as a carrier to regulate cerebral angiogenesis, so we propose the hypothesis that exosome miR-210 mediates HIF-1 α / VEGF/VEGFR2 pathway in electroacupuncture to reconstruct NVU homeostasis. In this project, chronic cerebral ischemia model rats were established, and the changes of learning and memory were observed by electroacupuncture Baihui and Shenting. The changes of prefrontal lobe-hippocampal white matter nerve fiber bundle were traced by fMRI-DTI, the changes of neurons, microglia and astrocytes were observed by laser confocal scanning, the changes of microvessel density were observed by, Western blot, the protein changes of HIF-1 α, VEGF, VEGFR2, APQ4 and ZO-1 were detected by, Western blot, and the morphological changes of exocrine body were observed by transmission electron microscope. The level of miR-210 was detected by qRT-PCR in an attempt to reveal the mechanism of electroacupuncture improving learning and memory impairment caused by chronic cerebral ischemia.