omega-3脂肪酸在围绝经期焦虑样小鼠中的抗焦虑作用及机制

Anti-anxiety effects and mechanism of omega-3 fatty acids in ovariectomized anxiety-like mice

目的:分析omega-3脂肪酸(n-3 PUFA)改善围绝经期焦虑样小鼠的焦虑行为作用并探讨其可能机制。方法:采用小鼠双侧卵巢摘除恢复1周后,进行慢性不可预知性应激的方法来制作围绝经期焦虑样小鼠模型。持续给予n-3 PUFA(10、20、60 mg/kg)14 d后通过大理石掩埋实验和高架十字迷宫实验验证其焦虑样行为。利用HPLC方法检测5-羟色胺(5-HT)、5-羟吲哚乙酸(5-HIAA)、去甲肾上腺素(NE)、多巴胺(DA)、二羟基苯乙酸(Dopac)神经递质及其代谢产物的含量来研究n-3 PUFA抗焦虑的相关机制。结果:持续给予围绝经期焦虑样小鼠n-3 PUFA(20、60 mg/kg)治疗后,有效地降低模型小鼠大理石掩埋的数量(P<0.05);n-3 PUFA(20、60 mg/kg)治疗显著地增加模型小鼠高架十字迷宫进入开臂的次数和时间(P<0.05)。HPLC检测结果显示,持续给予围绝经期焦虑样小鼠n-3 PUFA(20、60 mg/kg)治疗,明显升高前额叶皮层中5-HT、NE、DA的水平,降低5-HIAA/5-HT水平(P<0.05);持续给予围绝经期焦虑样小鼠n-3 PUFA(20、60 mg/kg)显著增加海马中5-HT、NE表达,减少5-HIAA/5-HT含量;提升下丘脑中5-HT、NE的含量(P<0.05)。结论:n-3 PUFA通过调节海马、前额叶皮层和下丘脑中的神经递质及其代谢产物含量改善围绝经期焦虑样小鼠的焦虑样行为。

Objective: To analyze the anti-anxiety effect of omega-3 polyunsaturated fatty acids(n-3 PUFA) in ovariectomized mice subject to unpredictable chronic stress and to reveal its mechanism. Methods: Chronic unpredictable stress was performed 1 week after bilateral ovarian ablation in mice to establish the model of menopausal anxiety. Using classical anxiety behavior tests(e marble-burying test and elevated plus maze test) to verify the anti-anxiety effect of chronic administration of n-3 PUFA(10, 20, 60 mg/kg) for 14 days. The mechanism of antianxiety of n-3 PUFA was investigated by HPLC method to detect the contents of 5-hydroxytryptamine(5-HT), 5-hydroxyindoleacetic acid(5-HIAA), noradrenaline(NE), dopamine(DA), dopac neurotransmitters and their metabolites. Results: Chronic administration of menopausal anxiety-like mice with n-3 PUFA(20, 60 mg/kg) effectively decreased the number of buried marbles and elevated the number and time to open arm at elevated plus maze test(P<0.05). HPLC results showed that chronic administration of menopausal anxiety-like mice with n-3 PUFA(20, 60 mg/kg) significantly affected 5-HT, 5-HIAA/5-HT, NE, DA in prefrontal cortex(P<0.05) and also significantly improved the concentration of 5-HT, 5-HIAA/5-HT, NE in hippocampus(P<0.05) and regulated the level of 5-HT, NE in hypothalamus(P<0.05). In summary, the possible mechanism of n-3 PUFA involves regulating neurotransmitters and its metabolite pathways in hippocampus, prefrontal cortex and hypothalamus. Conclusion: n-3 PUFA is an ideal drug for treating menopausal anxiety through regulating the neurotransmitters and its metabolites in hippocampus, prefrontal cortex and hypothalamic.