基于GABA能神经系统探究淫羊藿次苷Ⅱ的抗抑郁作用及机制

Exploration of antidepressant effect and mechanism of icarisideⅡbased on GABAergic nervous system

目的基于γ氨基丁酸(GABA)能神经系统研究淫羊藿次苷Ⅱ(ICSⅡ)的抗抑郁作用及潜在机制。方法将雄性昆明小鼠分为对照组(C组,10只)和造模组(50只),造模组小鼠以慢性不可预知温和应激法复制抑郁模型。刺激21 d后,将造模组小鼠随机分为抑郁模型组(NS组)、阳性对照药组[ECS组,草酸艾司西酞普兰15 mg/(kg·d)]和ICSⅡ低、中、高剂量组[ICSⅡ-L、ICSⅡ-M、ICSⅡ-H组,ICSⅡ10、20、30 mg/(kg·d)],每组10只。各药物组小鼠灌胃相应药物,每天1次,连续14 d。检测各组小鼠的糖水偏爱率、运动总距离、悬尾实验和强迫游泳实验的静止不动时间,观察其海马CA3区神经元及尼氏体形态,检测海马组织中GABA、谷氨酸(Glu)含量、GABA/Glu比值及GABA能神经系统相关蛋白(GABA A受体α1、GABA B受体1、GABA囊泡转运体、谷氨酸脱羧酶67、GABA膜转运体3)的表达情况。结果与C组比较,NS组小鼠糖水偏爱率显著降低,运动总距离显著缩短,悬尾实验和强迫游泳实验的静止不动时间均显著延长(P<0.05);海马CA3区的神经元形态不规则且尼氏体减少,结构完整的神经元数量显著减少(P<0.05);海马组织中Glu含量显著升高,GABA含量、GABA/Glu比值和GABA能神经系统相关蛋白表达水平均显著降低(P<0.05)。与NS组比较,各药物组大鼠的抑郁样行为均有所改善,上述指标普遍逆转(P<0.05)。结论ICSⅡ能够改善抑郁模型小鼠的抑郁样行为,其机制可能与调节GABA、Glu平衡,增加GABA的合成、转运、释放以及调节相关受体的表达进而改善GABA能神经系统功能有关。

OBJECTIVE To explore the antidepressant effect and potential mechanism of icarisideⅡ(ICSⅡ)based on the GABAergic nervous system.METHODS The male Kunming mice were randomly divided into a control group(group C,10 mice)and a modeling group(50 mice).The depression model was induced by chronic unpredictable mild stress(CUMS)method in the modeling group.After 21 days of stimulation,the rats of modeling group were randomly divided into depression model group(NS group),positive control group[ECS group,oxalate escitalopram 15 mg/(kg·d)]and ICSⅡlow-dose,medium-dose and high-dose groups[ICSⅡ-L group,ICSⅡ-M group,ICSⅡ-H group;ICSⅡ10,20,30 mg/(kg·d)],with 10 mice in each group.Administration groups were given relevant medicine intragastrically,once a day,for 14 consecutive days.The sugar water preference rate,total exercise distance,immobility time in tail suspension and forced swimming experiments were detected in each group.The morphology of neurons and Nissl bodies in the hippocampal CA3 region were observed;the contents ofγ-aminobutyric acid(GABA)and glutamic acid(Glu),GABA/Glu ratio,and the expressions of GABAergic nervous system-related proteins(GABA A receptorα1,GABA B receptor 1,vesicular GABA transporter,glutamate decarboxylase 67,GABA membranal transporter 3)were detected in hippocampus.RESULTS Compared with group C,the sugar water preference rate and the total exercise distance significantly reduced in NS group,while the values of immobility time in the tail suspension test and forced swimming test were significantly prolonged(P<0.05).The morphology of neurons in the CA3 area of the hippocampus was irregular and the Nissl bodies were reduced,with a significant decrease in the number of structurally intact neurons(P<0.05);the content of Glu was significantly increased,while the content of GABA,GABA/Glu ratio,and the expressions of GABAergic nervous system-related proteins were significantly decreased(P<0.05).Compared with NS group,depression behavior in each administration group was improved,and the above indexes were mostly reversed(P<0.05).CONCLUSIONS ICSⅡcan improve depression behavior of depression model mice.The mechanisms may be associated with regulating the balance of GABA and Glu,increasing the synthesis,transport and release of GABA,and regulating the expressions of GABA-related receptors,so as to improve GABAergic nervous system.