深低温停循环（DHCA）脑损伤是影响患者预后最重要的因素，激活NLRP3炎性小体引起神经血管单元（NVU）焦亡是脑损伤的关键环节。我们前期的研究发现TLR4/NF-κB通路调控Occludin表达引起通透性增加致脑损伤，但关键机制尚未阐明。预实验发现lncRNA MEG3/miR-676具有分别与NF-κB 和NLRP3结合的潜在位点，因此我们推测lncRNA MEG3/miR-676参与调控TLR4/NF-κB/ NLRP3信号通路的激活，诱导Occludin降解和NVU焦亡，最终导致脑损伤。本研究拟联合使用siRNA、RIP、荧光素酶和腺病毒等技术在DHCA体外体内模型进一步验证这一推测，旨在探究lncRNA MEG3/miR-676对TLR4/NF-κB/NLRP3信号通路介导NVU焦亡的调控在DHCA脑损伤的机制，为寻找内源性调控靶向分子、开发新颖的脑保护策略提供理论依据。

Deep hypothermic circulatory arrest (DHCA) brain injury is the most important factor influencing the prognosis of patients. Activation of NLRP3 inflammasome causes neurovascular units (NVU) pyroptosis as a key link in brain injury. Our previous studies found that TLR4/NF-κB pathway regulates the expression of Occludin and causes increased permeability-induced brain injury, but the key mechanism has not yet been elucidated. Pre-experimental studies revealed that lncRNA MEG3/miR-676 has potential sites for binding to NF-κB and NLRP3, respectively, and therefore we speculated that lncRNA MEG3/miR-676 is involved in regulating the activation of TLR4/NF-κB/NLRP3 signaling pathways, inducing Occludin degradation and NVU pyroptosis caused brain damage. This study intends to use siRNA, RIP, luciferase, and adenovirus technologies in combination with DHCA in vitro models to further validate this hypothesis and to explore the role of lncRNA MEG3/miR-676 in mediating NVU against TLR4/NF-κB/NLRP3 signaling pathways. The mechanism of focal regulation in DHCA brain injury provides a theoretical basis for finding endogenously regulated targeting molecules and developing novel brain protection strategies.