舒郁宁心汤抗抑郁作用的实验研究
发布时间:2018-03-16 03:34
本文选题:抑郁症 切入点:舒郁宁心汤 出处:《中国人民解放军医学院》2012年硕士论文 论文类型:学位论文
【摘要】:【目的】应用国内外公认的孤养加慢性轻度不可预见性的应激抑郁大鼠模型,研究治疗抑郁症有效方剂“舒郁宁心汤”的抗抑郁作用及可能的抗抑郁机理,为该药下一步临床应用及开发打下基础。 【方法】建立抑郁大鼠模型,60只SD大鼠随机分为6组:空白对照组、模型组、舒郁宁心汤高、中、低剂量组、氟西汀组,每组10只。造模成功后进行21天药物干预。采用敞箱实验观察大鼠行为学变化;采用免疫组化方法观察大鼠海马区BDNF和TrkB表达的变化;采用HE染色观察大鼠海马神经元细胞数量及形态结构的变化;采用TUNEL法检测大鼠海马神经元细胞凋亡数量;采用免疫组化方法观察大鼠海马凋亡调控蛋白Bcl-2和Bax表达的变化。 【结果】 1、造模后,模型组大鼠毛色粗糙、精神状态不佳、修饰次数、在中央格停留时间较正常对照组下降,,敞箱实验水平得分、垂直得分较正常对照组明显下降(P0.01),提示造模成功;经21天药物干预后,氟西汀组、舒郁宁心汤高、中、低剂量组大鼠的敞箱实验水平得分、垂直得分均较模型组显著提高(P0.01)。 2、舒郁宁心汤高、中、低组和氟西汀组大鼠海马BDNF和TrkB阳性表达平均光密度值高于模型组(P0.01、P0.05)。 3、HE染色可见模型组大鼠海马CA1区、CA3区神经元细胞与正常对照组比,数量减少,排列稀疏、少量细胞核有变形和固缩。 4、舒郁宁心汤高剂量组、中剂量组和氟西汀组大鼠海马Bax蛋白阳性表达低于模型组(P0.01),而Bcl-2蛋白阳性表达则高于模型组(P0.05)。 5、模型组大鼠海马凋亡细胞较正常组多(P0.01);舒郁宁心汤高、中、低剂量组和氟西汀组海马凋亡细胞较模型组少(P0.01)。 【结论】动物行为学结果显示:舒郁宁心汤对抑郁模型大鼠有抗抑郁作用,其作用机制与提高抑郁模型大鼠海马脑源性神经营养因子的含量,调节凋亡调控基因Bcl-2和Bax来减少海马神经元细胞凋亡有关。
[Abstract]:[objective] to study the antidepressant effect and possible antidepressant mechanism of Shuyu Ningxin decoction, an effective prescription for depression, in rats with chronic mild unpredictable stress depression, which is recognized at home and abroad. To lay a foundation for the next clinical application and development of the drug. [methods] Sixty SD rats with depression were randomly divided into six groups: blank control group, model group, high, middle and low dose of Shuyu Ningxin decoction, fluoxetine group. 10 rats in each group were treated with drugs for 21 days after successful modeling. The behavioral changes of rats were observed by open box experiment and the expression of BDNF and TrkB in hippocampus of rats were observed by immunohistochemical method. The number and morphology of hippocampal neurons in rats were observed by HE staining, the apoptosis of hippocampal neurons was detected by TUNEL method, and the expression of apoptosis-regulating proteins Bcl-2 and Bax in hippocampus of rats was observed by immunohistochemical method. [results]. 1. After modeling, the rats in the model group were rough in color, poor in mental state, modified times, decreased in the central space residence time, and the scores of open box test level and vertical score were significantly lower than those of the normal control group (P 0.01), which indicated that the model was successful; After 21 days of drug intervention, fluoxetine group, Shuyu Ningxin decoction group, medium, low dose groups of open box experimental level scores, vertical scores were significantly higher than the model group (P 0.01). 2, the average optical density of BDNF and TrkB positive expression in the hippocampus of the rats in the high, middle, low and fluoxetine groups was higher than that in the model group. 3HE staining showed that compared with the normal control group, the number of neurons in the hippocampal CA1 area of the model group was reduced, the number of neurons was sparse, and a few nuclei were deformed and pyknotic. 4. The positive expression of Bax protein in hippocampus of rats in high dose group, middle dose group and fluoxetine group was lower than that in model group, while the positive expression of Bcl-2 protein was higher than that in model group. 5. The apoptotic cells in hippocampus of the model group were more than those of the normal group, and the apoptotic cells in the hippocampus of the model group were higher than those of the normal group, and the apoptotic cells in the hippocampus of the low and middle dose groups and fluoxetine group were less than those in the model group. [conclusion] the results of animal behavior showed that Shuyu Ningxin decoction had antidepressant effect on depression model rats, and its mechanism was related to increasing the content of brain-derived neurotrophic factor in hippocampus of depression model rats. Regulation of apoptosis-regulating genes Bcl-2 and Bax to reduce apoptosis of hippocampal neurons.
【学位授予单位】:中国人民解放军医学院
【学位级别】:硕士
【学位授予年份】:2012
【分类号】:R285.5;R749.4
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