黄精皂苷对慢性应激抑郁大鼠大脑皮层5-HT_(1A) R-β-arrestin2-akt信号通路的影响

Effect of SRP on 5-HT_(1A) R-β-arrestin2-akt signaling pathway in rats with chronic stress induced depression

目的探讨黄精皂苷(SRP)对慢性应激抑郁模型大鼠行为学的影响及部分机制。方法 60只SD大鼠随机均分为正常组、模型组、SRP(400、200、100 mg/kg)组和氟西汀(2 mg/kg)组。采用7种不同应激方法建立大鼠慢性应激抑郁模型,观察大鼠行为学指标变化;免疫组化法测定大脑皮层区5-羟色胺1A受体(5-HT1AR)的表达;Western blot法分析大脑皮层区5-HT1AR、β-arrestin2、akt蛋白表达水平。结果应激刺激后,与正常组相比,模型组大鼠体重降低、自主活动次数减少,处于抑郁状态。免疫组化法及Western blot法结果显示,与正常组相比,模型组大脑皮层5-HT1AR表达降低,β-arrestin2、akt表达升高(P<0.05),而SRP组可以逆转这种现象(P<0.05,P<0.01)。结论中药SRP的抗抑郁作用可能与调节5-HT1AR/β-arrestin2/akt信号通路有关。

Objective To explore the anti-depressive effect of saponins of Rhizoma Polygonati （SRP） on behaviors test in rats with chronic stress and possible mechanism. Methods Sixty SD rats were randomly divided into six groups： normal group, model group, SRP （400,200, 100 mg/kg） groups, and fluoxetine （2 mg/kg） group. The model group was established by chronic unpredictable mild stress after 28 days. Behavioral indice were observed during and after the experiments. The protein levels were measured by Western blot and immunohistochemical analysis. Results After chronic stress stimulation, the behavioral indice showed an obvious depressive state in rats of depression model group as compared with normal control. In model group, the expression of 5-HTIAR was remarkably reduced, and the expression of β-arrestin2 and akt were increased compared to the normal group （ P 〈 0.05 ）. Moreover, compared with model group, SRP treated groups could reverse this phenomenon （P 〈 0. 01 ,P 〈 0.05）. Conclusion SRP can up-regulate the expression of 5-HTIAR and down-regulate the expression of β-arrestin2 and akt in cerebral cortex, which may be one of the mechanisms of SRP improvement of anti-depression.