蛇床子素对催产素受体沉默大鼠皮质区神经递质及焦虑抑郁行为的影响

Effects of Osthole on Cortical Neurotransmitters and the Anxiety-and Depresion-Like Behaviors in the Oxytocin Receptor-Silencing Rats

目的:探讨皮质区单胺类、氨基酸类和胆碱类神经递质与基底前脑催产素受体间相关性,阐明蛇床子素对催产素受体(oxytocin receptor,OTR)神经递质信号途径的作用及其对焦虑抑郁样行为的影响。方法:利用RNA干扰技术沉默大鼠基底前脑OTR,运用高架十字迷宫和强迫游泳实验观察蛇床子素对焦虑抑郁样行为的作用,运用QOrbitrap高分辨液质联用检测大鼠脑皮质区神经递质含量变化。结果:在高架十字迷宫中,OTR沉默组大鼠进入开放臂次数、停留时间明显减少(P<0.05),蛇床子素(12.5 mg·kg^(-1))干预后可增加大鼠进入开放臂次数和停留时间(P<0.01)。强迫游泳结果显示,与对照组相比,OTR沉默组大鼠不动时间延长(P<0.05),与OTR沉默组比,蛇床子素(12.5、25 mg·kg^(-1))能缩短不动时间(P<0.05)。OTR沉默组脑部皮质区的多巴胺(dopamine,DA)和L谷氨酸(Lglutamate,Glu)比对照组水平高(P<0.05),5羟色胺(5hydroxytryptamine,5HT)、γ氨基丁酸(γaminobutyric acid,GABA)、乙酰胆碱(acetylcholine,Ach)比对照组下降(P<0.05);蛇床子素(12.5 mg·kg^(-1))可下调DA水平(P<0.05),上调5HT、GABA和Ach水平(P<0.05)。蛇床子素(25 mg·kg^(-1))上调5HT和Ach水平(P<0.05)。结论:基底前脑OTR可能参与调控皮质神经递质,蛇床子素对基底前脑OTR沉默大鼠的焦虑抑郁行为有改善作用,其机制可能与基底前脑OTR皮质神经递质之间的信号网络有关。

Objective:To explore the role of oxytocin receptor(OTR)in regulating anxietyand depressionlike behaviors and monoamine,amino acids and choline neurotransmitters in the cerebral cortex.And to investigate the effects of osthole on neurotransmitters in OTR silencing rats.Methods:OTR silencing rats were established via short hairpin RNA(shRNA).Elevated plus maze and forced swimming test were used to observe the effect of osthole on anxietyand depression-like behaviors.Q-Orbitrap HPLC-HRMS was applied to detect neurotransmitters in the cerebral cortex of rats.Results:In the elevated plus maze,the number of entering the open arms and the residence time in the open arms were significantly reduced in the OTRshRNA rats compared with the control group(P<0.05).Osthole(12.5 mg·kg^(-1))treatment increased the number of entering the open arms and the residence time in the open arms compared with the OTRshRNA group(P<0.01).Forced swimming test showed that the OTRshRNA group rats were immobile for longer than the control group(P<0.05).The immobile time in the osthole(12.5 mg·kg^(-1) and 25 mg·kg^(-1))groups were reduced than that in the OTRshRNA group(P<0.05).Compared with the control group,the levels of dopamine(DA)and Lglutamic acid in the cerebral cortex of the OTRshRNA group were higher(P<0.05),and the levels of 5hydroxytryptamine(5HT),gamma aminobutyric acid(GABA),and acetylcholine(Ach)were significantly lower(P<0.05).Osthole(12.5 mg·kg^(-1))reduced the level of DA,and increased the level of 5HT,GABA and Ach(P<0.05),whereas osthole(25 mg·kg^(-1))increased the level of 5HT and Ach(P<0.05).Conclusions:Osthole could influence neurotransmitters in the cerebral cortex,and attenuate anxietyand depressionlike behaviors,which may be through regulating the OTR pathway.It provides a new direction and basis for the research in central nervous system disorders,such as depression.