逆转hnRNPA2/B1-SG水凝胶相变抑制MCI大鼠术后神经认知功能障碍（PNCD）研究及Kapβ2的驱动机制

轻度认知功能障碍（MCI）是术后神经认知功能障碍（PNCD）高发人群，加速向痴呆进程，亟需阐明机理并找到有效防治策略。前期发现随MCI-痴呆加重，核内不均一核糖核蛋白A2/B1（hnRNPA2/B1）核-质转移并在胞质积聚（Front Aging Neurosci），因此推测胞质hnRNPA2/B1液-液相分离加剧、引发应激颗粒（SG）水凝胶相变是PNCD关键机制。Kapβ2特异识别hnRNPA2/B1携带入核并恢复其功能、解聚SG。本项目制作MCI大鼠骨折切开内固定模型，培养低氧神经元，应用达到全身麻醉效能七氟烷、丙泊酚、地氟烷，从颅内血管功能、PNCD、fMRI、hnRNPA2/B1表达及功能、SG水凝胶相变测定，探讨hnRNPA2/B1-SG水凝胶相变通路在PNCD发生机制中关键作用及正调控Kapβ2防治PNCD可行性，为痴呆高转化率MCI患者围手术期神经功能保护及康复提供新思路。

Mild cognitive impairment (MCI) is a high incidence population of postoperative neurocognitive impairment (PNCD), which accelerates the process of MCI to dementia. It is necessary to clarify the mechanism and find effective prevention and treatment strategies. In the previous studies, we found that with the aggravation of MCI- dementia, the heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNPA2/B1) occurred nuclear cytoplasm transfer and accumulated in the cytoplasm (published in “Front Aging Neurosci” ). We speculated that the liquid-liquid phase separation of cytoplasmic hnRNPA2/B1 aggravates and triggers the stress granules (SG) hydrogel phase transition were the key mechanisms of PNCD. Kapβ2 can specifically recognize hnRNPA2/B1 and restore its function and depolymerize SG. Therefore in this study, MCI rat open reduction and internal fixation of fracture model was made and primary neuron was cultured. The depth of general anesthesia was achieved by sevoflurane, propofol or desflurane. The key roles of hnRNPA2/B1-SG hydrogel phase transition pathway in the pathogenesis of PNCD, the prevention and control feasibility by positive regulated Kapβ2 were discussed from the aspects of intracranial vascular function, PNCD, fMRI, hnRNPA2/B1 expression and function, and SG hydrogel phase transition. The present study will provide a new idea for the perioperative protection and rehabilitation of neurological function of MCI patients who have the high conversion rate to dementia.