ALDOA对急性缺血性脑卒中脑保护的调控作用及分子机制研究

急性缺血性脑卒中（AIS）后脑功能保护是脑神经科学研究的热点。我们的前期研究发现醛缩酶A（ALDOA）和基质金属蛋白酶（MMPs）在AIS患者血清中同时升高，且与脑神经损伤和修复密切相关。有研究报道HIF-1α能调控ALDOA及MMPs的表达，促进微小血管的重生和塑造。而我们的预实验结果也显示ALDOA可能通过保持HIF-1α的稳定性，上调MMPs的表达，但其分子机制尚不清楚。因此，我们推测：ALDOA可能通过HIF-1α的介导，增强MMPs的表达，促进脑微小血管的新生和侧枝循环的建立，从而能够对卒中后脑功能保护起到积极的作用。本项目拟构建AIS小鼠疾病模型和细胞缺氧模型，通过敲低或过表达ALDOA研究ALDOA/HIF-1α轴对MMPs表达的调控机制，揭示ALDOA对AIS脑功能保护的影响。旨在从卒中后血管新生的调控及机制方向，为AIS的防治提供新靶点。

Cerebral protection after acute ischemic stroke（AIS）is the research hotspot of neuroscience. It has been found that both aldolase A (ALDOA) and matrix metalloproteinases (MMPs) are elevated in the serum of AIS patients in our previous work, and which are closely related to nerve injury and repair. The most recent accomplishments have indicated that HIF-1α can regulate the expression of ALDOA and MMPs, while promoted the regeneration and reconstruction of microvessels. Our preliminary results may show that ALDOA may possibly maintain the stability of HIF-1α to up-regulate the expression of MMPs, however, the molecular mechanism needs a further study. Therefore, we speculated that ALDOA could potentially be mediated by HIF-1α to enhance the expression of MMPs, resulting in the regeneration and reconstruction of microvessels to improve the compensatory circulation, which eventually promoted brain function repair after AIS. This project will study the role of ALDOA on AIS pathological development through the AIS mice disease model and hypoxia cell culture model by knocking-down or over-expressing ALDOA, being designed to clarify the regulatory mechanism of ALDOA / HIF-1α axis on the expression of MMPs, and reveal the role of ALDOA in cerebral protection after AIS, which is to be hoped to provide a new target for the prevention and treatment of AIS from the major orientation of effective control and regulatory mechanism to be put in place for post-stroke angiogenesis.