逍遥散对CUMS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 of Xiaoyaosan on PI3K/AKT signaling pathway in hippocampal CA1 region of CUMS ratsZhou xueming 1 Yin yajing1 Changzhuo1 Liu chenyue2 Deng he1 Liang biyue1 Tan zengde3 Sui fangyu1

Purpose: The purpose of this study is to explore the effect of Xiaoyaosan on the metabolism of glutamate, and how to regulate the PI3K/AKT signal pathway.Methods: Rats were randomly divided into the control, CUMS, Xiaoyaosan, fluoxetine groups. Chronic unpredictable mild stress (CUMS) was used to induce a rat model of depression. The above groups were given double steam water, double steam water, Xiaoyao powder liquid and fluoxetine solution for 3 consecutive weeks. After that, behavioral observation and related indicators were detected. The open field test (OFT) and sucrose preference test (SPT) were used to assess the antidepressant effects of Xiaoyaosan. Then, 5-HT and NE level was detected by ELISA and the glutamate was detected by colorimetry. The RNA level of NR2B and PI3K were detected by RT-Qpcr, and the expression of NR2B, PI3K, P-AKT and Akt in hippocampal CA1 region was detected by western blot.Results: Xiaoyaosan decreased the level of glutamate in the hippocampal CA1 area and increase 5-HT and NE in CUMS rats. Furthermore, Xiaoyaosan increased the expression of NR2B, PI3K and the P-AKT/AKT ratio in the hippocampal CA1 region in the CUMS rats.Conclusions: Xiaoyaosan can significantly improve the depression-like behavior of chronic stress stimulated rats. The mechanism may be related to the enhancement of PI3K/Akt signaling pathway activity by decreasing the excitatory toxicity of glutamate.