电针对异氟醚诱导阿尔茨海默样病小鼠海马区PI3K/Akt信号通路的影响

Acupuncture on hippocampus PI3K/Akt signaling pathway against AD-like disease induced by isoflurane in mice

目的观察电针对异氟醚诱导阿尔茨海默(AD)样病小鼠海马区PI3K/Akt信号通路的影响。方法6月龄阿尔茨海默病转基因小鼠24只,随机分成3组:对照组(C组),异氟醚组(I组)、电针组(E组),每组8只。电针组在造模前3天行电针预处理。采用1.2%异氟醚连续吸入4 h复制异氟醚诱导AD样病小鼠模型,Y迷宫法检测小鼠的空间学习记忆能力;于造模后7 d取小鼠海马组织,TUNEL法检测海马CA1区神经元凋亡;免疫印迹法检测海马PI3K、Akt蛋白表达情况。结果与C组比较,实验组小鼠训练达标时间、学习次数、神经元凋亡光密度值均升高,PI3K、Akt蛋白表达下降,差异有统计学意义(P<0.05);与I组比较,E组小鼠训练达标时间、学习次数、神经元凋亡光密度值降低,PI3K、Akt蛋白表达升高,差异有统计学意义(P<0.05)。结论电针可通过激活海马区PI3K/Akt信号通路表达,减少海马CA1区神经元凋亡,从而抑制异氟醚诱导的AD样病小鼠学习记忆能力减弱,这可能是电针防治异氟醚神经毒性的作用机理之一。

Objective To evaluate the effect of acupuncture on hippocampus PI3 K/Akt signaling pathway against AD-like disease induced by isoflurane in mice. Methods Twenty-four 6-month-old APPswe/PS1 d E9 double transgenic mice were randomly assigned to three groups（ n = 8） ： control group（ Group C）,isoflurane group（ Group I） and electroacupuncture group（ Group E）. Electroacupuncture treatment was implemented for 3 days before isoflurane exposure. Models were copy by continuous inhalation of 1. 2% isoflurane for 4 hours. Y maze was used for detect the spatial learning memory; Hippocampal tissues were taken out 7 days after modeling and neuronal apoptosis was detected by TUNEL staining. Protein expressions of PI3 K and Akt were analyzed by western blot. Results Compared with Group C,the compliance training time,numbers of learning and optical density of neuronal apoptosiss were significantly increased（ P〈0. 05）,thus expressions of PI3 K and Akt significantly decreased（ P〈0. 05） in Group I and Group E. Compared with Group I. Conclusion Inhalation of 1. 2% isoflurane can lead to spatial memory decline,increased neuronal apoptosiss in the hippocampus in APPswe/PS1 d E9 double transgenic mice. Electroacupuncture can reduce this side effect through the PI3 K/Akt signaling pathway in the hippocampus,which may be one of the mechanisms which electroacupuncture can prevent neurotoxicity induced by isoflurane.