术后神经认知障碍已成为临床上一个亟待解决的重要问题，但发病机制不清。我们先前的研究发现，术后肠粘膜色氨酸代谢关键酶IDO过度表达致外周血犬尿氨酸水平增高，通过中性氨基酸转运体进入中枢并影响胆碱能神经功能是老年小鼠术后学习和记忆能力减退的关键，但肠粘膜IDO过度表达的机制不明。预实验结果提示老年小鼠术后肠粘膜3型天然淋巴样细胞(ILC3s)内芳香烃受体(AHR)激活，ILC3s增殖并释放IFN-γ。据此提出假说：术后肠道菌群紊乱产生大量AHR配体，激活ILC3s中的AHR，导致ILC3s增殖并释放IFN-γ等炎症因子，后者上调并激活肠粘膜IDO，最终引起外周血犬尿氨酸浓度增高和小鼠学习和记忆能力下降。本研究拟采用老年小鼠胫骨骨折内固定模型，应用IFN-γ中和抗体和ILC3s特异AHR敲除小鼠等手段来验证上述假说。本课题从肠道免疫的角度阐释术后神经认知障碍的机制，为其临床上的防治提供新的靶点。

Postoperative neurocognitive disorder has become an important clinical issue to be solved urgently, but its pathogenesis is still unclear. Our previous study found that the overexpression of IDO, a key enzyme of intestinal tryptophan metabolism after surgery, resulted in the elevated level of kynurenine in blood, and entered the central nervous system via neutral amino acid transporters and affected cholinergic nerve function, which was the key to the postoperative learning and memory decline in elderly mice, but the mechanism of the overexpression of IDO was unknown.The results of the preliminary experiment suggested that after surgery aromatic hydrocarbon receptor (AHR) activated, the intestinal group 3 natural lymphocytes (ILC3s) proliferated significantly and IFN-γ increased. Thus we get the hypothesis that the intestinal microflora disorders caused by surgery increase the ligands of AHR, thereby activating AHR and promoting the proliferation of intestinal ILC3s. The inflammatory factors released by the latter, such as IFN-γ, activate IDO and upregulate the concentration of kynurenine in the blood, leading to a decline in learning and memory eventually. This study intends to use the tibial fracture fixation model in elderly mice, IFN-γ neutralizing antibody and ILC3s specific AHR knockout mice to prove the hypothesis. In this study, we try to explain the mechanism of postoperative neurocognitive disorder from the perspective of intestinal immunity, providing a new target for clinical prevention and treatment.