依达拉奉调控PI3K/Akt信号通路抑制七氟烷致海马神经元凋亡

Edaravone inhibits sevoflurane-induced hippocampal neuron apoptosis by activating the PI3K/Akt signaling pathway

目的探讨依达拉奉对七氟烷致海马神经元凋亡及对PI3K/Akt信号通路影响。方法将80只成年昆明小鼠随机分为正常组、七氟烷组、七氟烷+依达拉奉组及LY294002+七氟烷+依达拉奉组,每组20只。正常组:小鼠不做处理;七氟烷组:小鼠每天给予1h吸入1.5%七氟烷;七氟烷+依达拉奉组:小鼠每天尾静脉注射依达拉奉3 mg·kg^(-1)后,给予1h吸入1.5%七氟烷;LY294002+七氟烷+依达拉奉组:小鼠每天尾静脉注射依达拉奉3 mg·kg^(-1)和LY2940020.3 mg·kg^(-1)给予1h吸入1.5%七氟烷。总共麻醉14 d。麻醉结束后,采用TUNEL法检测海马神经元凋亡的情况,采用Y迷宫检测各组小鼠学习记忆能力,Western blotting检测海马神经元细胞中磷脂酰肌醇激酶(PI3K)、磷酸化蛋白激酶B(p-AKT)、B淋巴细胞瘤-2基因(Bcl-2)和Bcl-2相关X蛋白(Bax)蛋白表达。结果与正常组相比,七氟烷组小鼠海马神经元凋亡率升高(P<0.05),学习、记忆能力下降(P<0.05),PI3K、p-Akt和Bcl-2的蛋白表达下降(P<0.05),Bax蛋白表达升高(P<0.05)。与七氟烷组相比,七氟烷+依达拉奉组小鼠海马神经元凋亡率降低(P<0.05),学习、记忆能力上升(P<0.05),PI3K、p-Akt和Bcl-2的蛋白表达升高(P<0.05),Bax蛋白表达下降(P<0.05)。PI3K抑制剂LY294002与依达拉奉联合注射后,逆转了依达拉奉的上述作用。结论依达拉奉通过激活PI3K/Akt信号通路抑制七氟烷致海马神经元凋亡。

Objective To investigate the effect of edaravone on hippocampal neuron apoptosis induced by sevoflurane and its effect on PI3 K/Akt signaling pathway.Methods Eighty adult kunming mice were randomly divided into normal group,sevoflurane group,sevoflurane+edaravone group,and LY294002+sevoflurane edaravone group,20 in each group.Normal group:mice were left untreated;sevoflurane group:mice were given 1.5%sevoflurane inhalation for 1 hour every day;sevoflurane+edaravone group:mice were injected with edaravone 3 mg·kg^(-1)·d-1 Then,inhaled1.5%sevoflurane for 1 h;LY294002+sevoflurane+edaravone group:mice were injected with edaravone 3 mg·kg^(-1)and LY2940020.3 mg·kg^(-1) in the tail vein every day,and inhaled 1.5%sevoflurane for 1 h.The total anesthesia time was 14 days.After anesthesia,TUNEL was used to detect hippocampal neuron apoptosis,Y maze was used to detect the learning and memory abilities of mice in each group,and Western blotting was used to detect phosphatidylinositol kinase(PI3 K),phosphorylated protein kinase B(p-AKT),B lymphoma-2 gene(Bcl-2)and Bcl-2 related X protein(Bax)protein expression in hippocampal neurons.Results Compared with the normal group,the apoptotic rate of hippocampal neurons in the sevoflurane group increased(P<0.05),learning and memory abilities decreased(P<0.05),and protein expressions of PI3 K,p-Akt and Bcl-2 decreased(P<0.05),Bax protein expression increased(P<0.05).Compared with the sevoflurane group,the apoptosis rate of hippocampal neurons in the sevoflurane+edaravone group was reduced(P<0.05),and their learning and memory abilities were increased(P<0.05).PI3 K,p-Akt and Bcl-2 protein expression increased(P<0.05),and Bax protein expression decreased(P<0.05).The combined effects of LY294002 and edaravone reversed the aforementioned effects of edaravone.Conclusion Edaravone can inhibit the apoptosis of hippocampal neurons induced by sevoflurane by activating the PI3 K/Akt signaling pathway.