摘要目的:探讨艾司氯胺酮对腹部手术后小鼠海马神经元脑源性神经生长因子(BDNF)通路蛋白表达和树突棘密度的影响。方法:24只8周龄雄性C57BL/6小鼠随机分为3组——正常对照组(Control)、异氟烷手术组(Iso)、艾司氯胺酮手术组(Esk)，分别给予无处理，异氟烷麻醉下开腹手术和艾司氯胺酮麻醉下开腹手术处理。术后第3天提取小鼠海马神经元进行高尔基染色和BDNF通路蛋白的蛋白质印迹法(Western blot)，观察并记录神经元树突棘密度和BDNF通路相关蛋白表达水平。组间比较采用单因素方差分析(ANOVA)，进一步两两比较采用SNK- q检验。 结果:Control组、Iso组和Esk组的BDNF相对灰度值分别为0.95±0.25、0.31±0.16和0.46±0.15，pTrkB/TrkB在Control组、Iso组和Esk组分别为1.39±0.15、0.42±0.11和0.43±0.10，差异均有统计学意义( F＝14.56、20.01，均 P<0.05)。Iso组和Esk组小鼠术后3 d海马神经元BDNF表达水平均显著低于Control组( P<0.05)，Iso组和Esk组小鼠术后3 d海马神经元TrkB的磷酸化水平均显著低于Control组( P<0.05)，Iso组和Esk组之间差异无统计学意义( P>0.05)。Control组、Iso组和Esk组的海马神经元树突棘密度分别为(8.93±2.01)、(4.11±1.64)、(4.08±1.72)个/10 μm，3组的海马神经元成熟伞状树突棘密度分别为(5.03±1.67)、(2.02±0.88)、(2.77±1.16)个/10 μm，差异均有统计学意义( F＝13.49、22.16，均 P<0.05)。Iso组和Esk组小鼠术后3 d海马神经元树突棘密度和成熟伞状树突棘密度均显著低于Control组( P<0.05)，Iso组和Esk组之间差异无统计学意义( P>0.05)。 结论:艾司氯胺酮联合腹部手术可降低小鼠术后3 d海马神经元BDNF表达水平和通路蛋白TrkB的磷酸化水平，并造成树突棘密度的减少。

abstractsObjective:To investigate the effect of esketamine on the hippocampal neuron brain derived neurotrophic factor (BDNF) pathway protein expression and dendritic spine density in mice undergoing abdominal surgery.Methods:Totally, 24 C57BL/6-8 weeks old male mice were randomly divided into control group, abdominal surgery in isoflurane anesthesia group (Iso) and abdominal surgery in esketamine anesthesia group (Esk). On the third day after surgery the mice hippocampal neurons were extracted to be stained by Golgi-Cox for dendritic spine calculation. The BDNF pathway protein expression level of the neurons was detected by Western blotting. One-way analysis of variance (ANOVA) was used for comparison between groups, and SNK- q test was used for further pairwise comparison. Results:The BDNF relative protein levels in control group, Iso group and Esk group were respectively 0.95±0.25, 0.31±0.16 and 0.46±0.15, and the pTrkB/TrkB level in control group, Iso group and Esk group were respectively 1.39±0.15, 0.42±0.11 and 0.43±0.10. The differences were statistically significant ( F=14.56, 20.01, all P<0.05). The BDNF expression and the TrkB phosphorylation level in hippocampal neurons were lower in Iso group and Esk group than in control group (all P<0.05), but there was no significant difference between Iso and Esk groups ( P>0.05). The dendritic spine density in hippocampal neurons in control group, Iso group and Esk group was respectively (8.93±2.01), (4.11±1.64), (4.08±1.72)/10 μm, and mushroom-type spines in the hippocampal neurons in three groups were respectively (5.03±1.67), (2.02±0.88), (2.77±1.16)/10 μm. There was significant difference ( F=13.49, 22.16, all P<0.05). The dendritic spine and mushroom spine density in hippocampal neurons were both thicker in control group than in Iso group and Esk group (all P<0.05), but there was significant difference between the Iso and the Esk groups ( P>0.05). Conclusion:Esketamine with abdominal surgery decreases the hippocampal neuron BDNF expression and TrkB phosphorylation level and dendritic spine density in mice 3 days after abdominal surgery.