刘海英 杨进国 曾文强 顾欣 朱辉

摘要  目的：觀察银杏叶提取物对七氟醚致认知功能的影响，并探讨其可能的作用机制。方法：将45只SD大鼠随机分为空白组、七氟醚组及干预组，每组15只。其中空白组不做任何干预措施，七氟醚组吸入七氟醚;干预组同样予吸入七氟醚后腹腔注射银杏叶提取物，用水迷宫比较各组大鼠学习记忆能力的变化，HE染色观察海马病理结构改变，免疫印迹法检测海马组织PI3K、Akt、p-Akt、Bcl-2、Bax表达水平的变化。结果：七氟醚组及干预组大鼠游泳轨迹和逃避潜伏期较空白组延长，差异有统计学意义（ P <0.05），其中干预组明显较七氟醚组改善，差异有统计学意义（ P <0.05）。空白组大鼠海马组织结构形态正常，七氟醚组及干预组大鼠海马组织均出现明显结构破坏，细胞排列错乱，神经元细胞出现明显变形缩小，其中干预组海马形态结构较七氟醚组改善。经过银杏叶提取物干预后大鼠海马组织PI3K、Akt磷酸化程度提高以及Bcl-2表达增加，抑制Bax的表达。结论：银杏叶提取物可明显提升七氟醚所致认知能力，其作用机制可能与抑制PI3K/Akt信号通路有关。

关键词  七氟醚;大鼠;认知;学习记忆能力;银杏叶提取物注射液;海马;机制;PI3K/Akt信号通路

Effects of Ginkgo Biloba Extract Injection on the Cognitive Function of Rats after Sevoflurane Anesthesia

LIU Haiying1，YANG Jinguo1，ZENG Wenqiang1，GU Xin2，ZHU Hui1

（1 Department of Anesthesiology，National Medicine Dongfeng General Hospital，Shiyan 442000，China; 2 Department of Cardiothoracic Surgery，the People′s Hospital of Shiyan 442000，China）

Abstract Objective： To observe the effects of Ginkgo Biloba extract on cognitive function induced by sevoflurane and explore its possible mechanism. Methods： A total of 45 SD rats were randomly divided into a blank group （ n =15），a sevoflurane group （ n =15） and an intervention group （ n =15）.Among them，the blank group did not take any interventions，the sevoflurane group inhaled sevoflurane，and the intervention group also received intraperitoneal injection of Ginkgo Biloba extract after inhaling sevoflurane.The changes of learning and memory ability of rats in each group were compared by water maze，and the pathological changes of hippocampus were observed by HE staining，Western blotting was used to detect the expression levels of PI3K，Akt，p-Akt，Bcl-2 and Bax in hippocampus. Results： 1） The swimming trajectory and escape latency period of rats in the sevoflurane group and the intervention group were longer than those in the blank group （ P <0.05），and those in the intervention group were significantly better than those in the sevoflurane group （ P <0.05）.2） HE staining showed that the hippocampal structure of rats in the blank group was normal，and the hippocampal tissue of rats in the sevoflurane group and the intervention group showed obvious structural destruction，disordered arrangement of cells and obvious deformation and shrinkage of neurons.The morphological structure of the hippocampus in the intervention group was better than that in the sevoflurane group.3） Western blotting showed that after the intervention of Ginkgo Biloba extract，the phosphorylation of PI3K and Akt and the expression of Bcl-2 in hippocampus were increased，and the concentration of Bax was inhibited. Conclusion： Ginkgo Biloba extract can significantly improve the cognitive function induced by sevoflurane，and its mechanism may be related to the inhibition of PI3K/Akt signal pathway.

Keywords  Sevoflurane; Rat; Cognition; Learning and memory ability; Ginkgo Biloba extract injection; Hippocampus; Mechanism; PI3K/Akt signal pathway

中图分类号：R283 文献标识码：A  doi： 10.3969/j.issn.1673-7202.2020.14.009

七氟醚以血气分配系数低、麻醉诱导速度快、麻醉深度易于控制、苏醒快速等特点被广泛应用于临床，但随着研究的不断深入有文献[1]揭示七氟醚可导致一过性认知障碍，其作用机制与PI3K/AKT信号通路有关，PI3K/AKT信号通路是经典的抗凋亡通路，故我们认为激活PI3K/AKT信号通路是改善术后认知障碍的途径。银杏叶提取物属于中药制剂，目前研究揭示其有利于脑损伤与记忆等功能的恢复，但作用机制尚不明了。银杏叶提取物改善认知是否通过PI3K/AKT信号通路进行介导？由此我们进行动物模型研究，以期探讨银杏叶提取物改善七氟醚引起认知障碍的可能机制。

1 材料与方法

1.1 材料

1.1.1 实验动物

选取45只SPF级SD雄性大鼠，购自湖北省动物研究中心（动物生产许可证号：SCXK（鄂）2016-0016），体质量220～250 g，平均体质量（230±10.5）g;鼠龄3～5个月，平均鼠龄（3.5±1.1）个月。……