Orexins/NLRP-1炎性通路在迷走神经电刺激对脑外伤昏迷大鼠促醒中的作用及机制研究

脑外伤昏迷后意识的恢复直接影响疾病的发展和转归。最新文献报道迷走神经电刺激（Vagus nerve stimulation，VNS）可以提高脑损伤昏迷患者的觉醒度，我们前期研究也发现VNS能够改善脑外伤昏迷大鼠的意识状态，其机制与上调orexins的表达有关。前期实验表明NLRP-1通路参与了脑外伤昏迷的发生和发展，且预实验发现orexins可抑制NLRP-1的表达，因此我们提出假设：VNS促醒机制可能是通过上调orexins抑制NLRP-1通路，进而降低神经炎症水平达到脑保护作用。为此，拟建立脑外伤昏迷大鼠和细胞模型，1)研究VNS促醒机制是否通过抑制NLRP-1通路；2）探讨orexins是否参与VNS调控NLRP-1通路；3）明确orexins如何抑制NLRP-1。本研究将在动物整体水平和细胞学水平上探讨VNS对脑外伤昏迷大鼠的促醒作用机制，从而为VNS促醒的临床应用提供理论依据。

Recovery of consciousness of paitents with traumatic brain injury critically influences the prognosis of patients. The latest literature reported that the wakefulness of comatose patients with brain injury can be improved by Vagus nerve stimulation (VNS) .Our previous studies also showed that the consciousness of the comatose rats with traumatic brain injury can be improved by VNS, and the mechanism is related to the upregulation of orexins expression. Pre-studies shown that NLRP-1 pathway participates in the occurrence and development of coma after traumatic brain injury, and preliminary experiment indicated that the expression of NLRP-1 can be inhibited by orexins.We hypothesize that the mechanisms of VNS causing wake-promotion may be mediated by upregulation of NLRP-1 pathway via orexins, and decreasing neuroinflammation, which eventually leads to brain protection. We will establish the coma model of rats and cell, objects: 1)to study whether VNS induces wake-promotion mediated by NLRP-1 pathway; 2)to discuss whether orexins involves in VNS regulating NLRP-1 pathway; 3)to clarify how orexins inhibites NLRP-1. This study will explore the mechanisms of VNS inducing wake-promotion in animal and cytology, so as to provide a theoretical basis for the clinical application of VNS.