目前研究认为炎症反应是发生脑外伤后认知功能障碍原因之一，但具体机制仍不明了。申请者前期研究成果一方面发现大黄有效成分可抑制脑外伤后神经炎症反应改善认知功能障碍，另一方面明确了脑铁蓄积能加重认知功能损害，而脑外伤后TLR4/MyD88炎症信号通路上调铁调素水平导致脑铁蓄积现已得到证实，阐明了铁与神经炎症的密切关系。因此研究大黄有效成分与脑铁代谢之间的关系可能是揭示其治疗脑外伤后认知功能障碍机制的钥匙，通过“大黄-神经炎症-铁-认知障碍”关系研究，探寻炎症反应介导的脑铁代谢紊乱是否是产生认知障碍的效应通路。项目拟构建人源细胞模型，评估大黄有效成分对铁外排转运的影响，同时脑外伤动物模型干预，早期磁共振分子影像学检测脑铁含量，后期行为学认知功能评价，进一步shRNA干扰铁调素对照研究，炎症因子芯片检验，明确大黄有效成分与脑铁代谢及脑外伤后认知功能障碍的关系，为促进脑外伤患者认知功能康复提供新思路。

At present, it is considered that inflammatory reaction is one of the causes of cognitive dysfunction after traumatic brain injury, but the specific mechanism is still unknown. Applicants previous research point out that rhubarb can inhibit the neuroinflammation reaction after traumatic brain injury and brain iron accumulation can cause cognitive impairment after traumatic brain injury. Hepcidin affects brain iron efflux has been confirmed through TLR4/MyD88 inflammatory signaling pathway.So we speculate that iron is the key point of cognitive dysfunction after traumatic brain injury in inflammatory mechanisms. Through a survey of the relationship between Rhubarb - nerve inflammation - iron - cognitive impairment, confirmed brain iron metabolism disorders mediated by inflammation may be the “common pathway”to produce cognitive disorders.In vitro research of this project to construct a human cell model, detection of iron efflux effect, in vitro biological function of rhubarb;according to the past research results of brain blast injury animal model, emodin blocking after traumatic brain injury and inflammatory signaling pathways, early molecular magnetic resonance imaging learn to assess changes in brain iron, late behavior evaluation of cognitive function, further shRNA iron regulating element control research, inflammation factor chip verification, to understand the relationship between cognitive dysfunction after inflammatory signaling,brain iron metabolism and traumatic brain injury, provide a new ideas to improve cognitive function after traumatic brain injury.