逍遥散对抑郁大鼠海马CA1区PI3K/AKT信号通路的调节作用研究

目的:本研究旨在探讨逍遥散通过调节PI3K/Akt信号通路进而改善由谷氨酸引起的兴奋性损伤的机制。方法:100只雄性SD大鼠随机分为正常组、模型组、逍遥散组和氟西汀组,利用CUMS方法造模成为抑郁模型大鼠,上述组别分别予以双蒸水、双蒸水、逍遥散药液、氟西汀溶液连续灌胃3周,后进行行为学观察及相关指标检测。采用旷场试验(OFT)和蔗糖偏好试验(SPT)评价逍遥散的抗抑郁作用;ELISA法测定海马组织中5-HT、NE水平;比色法检测各组大鼠海马CA1区谷氨酸水平;RT-qPCR检测海马CA1区NR2B、PI3K的mRNA水平;western blot检测海马CA1区NR2B、PI3K、P-AKT、Akt的蛋白表达。结果:逍遥散的体内干预可显著提高抑郁模型大鼠海马组织中的5-HT、NE水平、降低海马CA1区谷氨酸水平、增加了海马CA1区NR2B、PI3K及P-AKT/Akt比值,显著改善了大鼠的抑郁症状。结论:逍遥散可显著改善经慢性应激刺激后大鼠的抑郁样行为,其机制可能与降低谷氨酸兴奋性毒性,从而提高PI3K/Akt信号通路活性有关。

Regulation Effect of Xiaoyao Powder on PI3K/AKT Signaling Pathway in Hippocampal CA1 Region of CUMS Rats

Objective:To explore the mechanism of Xiaoyao Powder in improving glutamate-induced excitotoxicity by regulating PI3K/Akt signaling pathway.Methods:100 SD rats were randomly divided into the normal group,the model group,the Xiaoyao Powder group and the Fluoxetine group.The depression model was established by the method of chronic unpredictable mild stress(CUMS).After 3 weeks of corresponding interventions,ethology was observed and related indicators were detected.The open field test(OFT)and sucrose preference test(SPT)were used to assess the anti-depressant effects of Xiaoyao Powder.The levels of 5-HT and NE in hippocampus were detected by ELISA;the level of glutamate was detected by colorimetry;the mRNA expressions of NR2B and PI3K were detected by RT-qPCR;and the protein expressions of NR2B,PI3K,P-AKT and Akt in hippocampal CA1 region were detected by Western Blot.Results:Xiaoyao Powder decreased the level of glutamate and increase the levels of 5-HT and NE of the hippocampal CA1 area in CUMS rats.Furthermore,Xiaoyao Powder increased the expressions of NR2B,PI3K and P-AKT/Akt ratio in the hippocampal CA1 region in the CUMS rats.Conclusion:Xiaoyao Powder can significantly improve the depression-like behavior of CUMS.The mechanism may be related to the enhancement of PI3K/Akt signaling pathway activity by decreasing the excitatory toxicity of glutamate.