机构地区:[1]山东中医药大学中医药经典理论教育部重点实验室,济南250355 [2]山东中医药大学基础医学院,济南250355
出 处:《中国实验方剂学杂志》2012年第17期165-169,共5页Chinese Journal of Experimental Traditional Medical Formulae
基 金:国家重点基础研究发展计划(973计划)课题(2011CB505102);国家自然科学基金重点项目(30930110);山东省科技发展计划项目(2010GSF10290)
摘 要:目的:观察抑郁情绪大鼠模型给药血清对离体海马神经元γ氨基丁酸B2受体(GABABR2)蛋白表达的影响,初步探讨舒郁胶囊及其君药柴胡对抑郁情绪的干预作用和机制。方法:35只Wistar大鼠随机分为5组:正常组、模型组、舒郁组(0.51 g.kg-1)、柴胡组(0.4 g.kg-1)和氟西汀组(0.002 g.kg-1),采用28 d慢性温和刺激(CMS)制备抑郁情绪大鼠模型,治疗组造模的同时灌胃给药,通过大鼠体重、糖水摄入量、旷场实验对模型进行评价,评定模型复制成功后,制备各组大鼠血清,采用血清药理学方法,通过抑郁情绪模型大鼠各组血清干预大鼠原代海马神经元,应用蛋白免疫印迹技术,检测海马神经元GABABR2的蛋白表达。结果:与正常组大鼠相比,模型组体质量、糖水实验的糖水摄入、旷场实验总分均显著减少(P<0.01);而造模并分别给予舒郁、柴胡和氟西汀的大鼠较模型组大鼠体质量、糖水实验的糖水摄入、旷场实验总分显著增加(P<0.05,P<0.01)。蛋白免疫印迹结果显示,与正常组血清干预的海马神经元相比,模型血清组海马神经元GABABR2蛋白表达显著升高(P<0.01);造模并给予舒郁胶囊血清组和氟西汀血清组干预的大鼠海马神经元GABABR2蛋白表达较模型血清组显著降低(P<0.05),柴胡组有改善的趋势,但无显著性差异。结论:抑郁情绪模型大鼠血清可诱导大鼠海马神经元GABABR2蛋白表达上调,舒郁胶囊可能是通过降低海马神经元GABABR2蛋白表达发挥抗抑郁作用。Objective: Our aim was to investigate the protein changes of the expression of γ-aminobutyric acid B2 (GABAsR2) receptor in primary cultured rat hippocampus neurons, to explore the intervention mechanism of Shuyu capsule for treating depression emotion preliminarily. Method: We used the chronic mild stress (CMS) to establish the depression emotion (DE) model in rats, and then the rats were evaluated by sucrose intake, the body weight and open-field from beginning to the end for the model. Serum of rats in each group was collected and then added into the medium of vitro cultured hippocampus primary neurons. At last the expression of γ- aminobutyric acid B2 receptor was detected with Western blot respectively. Result: Compared with the normal group, the weight, the total score of open field test and the sucrose intake of preference test of rats in depression emotion model group lessened significantly (P 〈 0.01 ). On the other hand, compared with the depression emotion model group, the weight, the total score of open field test and the sucrose intake of preference test of rats in Shuyu capsule, bupleurum and fluoxetine treatment groups increased significantly (P 〈 0.05 or P 〈 0.01 ). Western blot demonstrated that the serum of model group rats obviously increased the protein levels of GABAs R2 (P 〈 0.01 ) , compared with the normal control group. While serum of the Shuyu capsule and fluoxetine treatment groups markedly decreased the protein levels of GABABR2 (P 〈 0.05) , the bupleurum group had no difference with the model group, but the trendhad improved. Conclusion: The serum of rats with depression emotion could induce the high expression of GABABR2, the Shuyu capsule may play antidepressants by reducing the expression of GABABR2 in primary cultured rat hippocampus neurons. The bupleurum also has a good antidepressant effect, but the effect is less than Shuyu capsule.
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