术后认知功能障碍（POCD）发病机制不明，目前药物疗效有限的原因与麻醉药作用机制复杂关系密切。因此，基于中枢胆碱能系统研究七氟烷致认知功能障碍的机制具有重要价值。课题组前期研究发现七氟烷损害新生期、老龄期大鼠学习记忆能力，引起新生期海马Aβ沉积。鉴于Aβ与中枢胆碱能系统关系密切，我们推测，七氟烷通过作用于中枢胆碱能系统，引起海马神经元改变、抑制LTP等最终引发行为学改变。所以，本项目首先建立新生期和老龄期大鼠吸入七氟烷模型，通过fMRI观察七氟烷对海马脑区功能活动的影响，然后观察海马神经元胞体和突触链接；在明确七氟烷损伤海马神经元和突触链接的基础上，再观察海马ChAT、ACh、α7nAChR、AChE变化，并通过AChE基因沉默技术观察ACh、α7nAChR的变化；最后观察海马电生理改变。本研究旨在探索七氟烷致中枢神经系统两个易损期认知功能障碍的海马多靶点机制，为POCD防治提供理论依据。

The mechanism of postoperative cognitive dysfunction（POCD） is still unclear, the reason of the limited therapeutic effect is closely related to the complex mechanism of anesthetics action presently.Hence,it is of great value to study on the mechanism of POCD induced by sevoflurane based on central cholinergic system. Our previous studies found that sevoflurane anesthesia may lead to impairment of learning and memory ability in neonatal rats and aged rats, and cause β-amyloid protein(Aβ) deposition in hippocampus in neonatal period. In view of the close relationship between Aβ and central cholinergic system, we speculate that sevoflurane might cause changes in hippocampal neurons ,inhibit LTP and finally trigger behavioral changes by affecting the central cholinergic system. Thus, this project is to observe the effects of sevoflurane on the functional activities of the hippocampus by functional magnetic resonance imaging(fMRI) and then observe the connections between hippocampal neurons and synapses according to establish sevoflurane inhalational anesthesia model in neonatal rats and in aged rats ; Observe changes of ChAT,Ach,α7nAChR and AChE in hippocampus after confirm the connections between hippocampal neurons and synapses damaged by sevoflurane,and observe changes of Ach and α7nAChR by AChE gene silencing;Lastly, electrophysiological changes of hippocampus will be observed. This study aims to explore the mechanism of multiple targets in hippocampus of sevoflurane anesthesia on POCD in the two vulnerable periods of the central nervous system and to provide basis for the prevention and treatment of POCD.