针刺干预创伤性脑损伤及其对TLR4/MyD88/TRIF介导的小胶质细胞活化的调控机制研究

创伤性脑损伤（TBI）发生过度神经炎症是引发中枢神经二次损伤的重要原因。神经炎症的主要效应细胞是小胶质细胞，受损神经元通过TLR4/MyD88/TRIF信号介导该细胞发生M1活化，持续的活化状态则引起过度神经炎症。神经炎症的主要中医病机为气机逆乱、瘀血阻滞脑络，具有行气活血祛瘀通络作用的针刺疗法可以有效治疗TBI神经炎症。我们前期发现针刺可以抑制TBI大鼠神经炎症，在研项目又发现其作用可能与TLR2信号有关，但其具体调控机制未知。因此我们提出假设，针刺可能通过调控TLR4/MyD88/TRIF通路及其下游的相关信号传导功能从而抑制小胶质细胞活化，调节过度的神经炎症。本项目将构建TBI大鼠模型，从TLR4/MyD88/TRIF信号介导的小胶质细胞活化表达等机制出发，探讨针刺疗法对TBI过度神经炎症的调控机制，为针刺治疗TBI的作用机制提供新的理论支持与研究思路。

Traumatic brain injury (TBI) excessive neuroinflammation is an important cause of secondary damage to the central nervous system. The main effector of neuroinflammation is microglia. The damaged neurons induce M1 activation by TLR4/MyD88/TRIF signaling, and the sustained activation causes excessive neuroinflammation. The mainly TCM pathogenesis of neuroinflammation is Qi movement chaos, Blood stasis brain meridian. Acupuncture therapy can treat TBI neuroinflammation effectively with moving Qi, activating Blood and resolving Stasis. We found that acupuncture can inhibit the neuroinflammation of TBI rats previously, and ongoing projects also found that its role may be related to the TLR2 signal, but the specific regulatory mechanism is unknown. Therefore, we hypothesize that acupuncture may inhibit the activation of microglia and regulate excessive neuroinflammation through the TLR4/MyD88/TRIF and its underlying signaling. This study will construct TBI rat model, from TLR4/MyD88/TRIF mediated activation of microglia, to explore the regulation mechanism of acupuncture therapy on TBI excessive neuroinflammation.