舒郁寧心湯抗抑郁作用的實(shí)驗(yàn)研究
本文選題:抑郁癥 切入點(diǎn):舒郁寧心湯 出處:《中國(guó)人民解放軍醫(yī)學(xué)院》2012年碩士論文 論文類型:學(xué)位論文
【摘要】:【目的】應(yīng)用國(guó)內(nèi)外公認(rèn)的孤養(yǎng)加慢性輕度不可預(yù)見(jiàn)性的應(yīng)激抑郁大鼠模型,研究治療抑郁癥有效方劑“舒郁寧心湯”的抗抑郁作用及可能的抗抑郁機(jī)理,為該藥下一步臨床應(yīng)用及開(kāi)發(fā)打下基礎(chǔ)。 【方法】建立抑郁大鼠模型,60只SD大鼠隨機(jī)分為6組:空白對(duì)照組、模型組、舒郁寧心湯高、中、低劑量組、氟西汀組,每組10只。造模成功后進(jìn)行21天藥物干預(yù)。采用敞箱實(shí)驗(yàn)觀察大鼠行為學(xué)變化;采用免疫組化方法觀察大鼠海馬區(qū)BDNF和TrkB表達(dá)的變化;采用HE染色觀察大鼠海馬神經(jīng)元細(xì)胞數(shù)量及形態(tài)結(jié)構(gòu)的變化;采用TUNEL法檢測(cè)大鼠海馬神經(jīng)元細(xì)胞凋亡數(shù)量;采用免疫組化方法觀察大鼠海馬凋亡調(diào)控蛋白Bcl-2和Bax表達(dá)的變化。 【結(jié)果】 1、造模后,模型組大鼠毛色粗糙、精神狀態(tài)不佳、修飾次數(shù)、在中央格停留時(shí)間較正常對(duì)照組下降,,敞箱實(shí)驗(yàn)水平得分、垂直得分較正常對(duì)照組明顯下降(P0.01),提示造模成功;經(jīng)21天藥物干預(yù)后,氟西汀組、舒郁寧心湯高、中、低劑量組大鼠的敞箱實(shí)驗(yàn)水平得分、垂直得分均較模型組顯著提高(P0.01)。 2、舒郁寧心湯高、中、低組和氟西汀組大鼠海馬BDNF和TrkB陽(yáng)性表達(dá)平均光密度值高于模型組(P0.01、P0.05)。 3、HE染色可見(jiàn)模型組大鼠海馬CA1區(qū)、CA3區(qū)神經(jīng)元細(xì)胞與正常對(duì)照組比,數(shù)量減少,排列稀疏、少量細(xì)胞核有變形和固縮。 4、舒郁寧心湯高劑量組、中劑量組和氟西汀組大鼠海馬Bax蛋白陽(yáng)性表達(dá)低于模型組(P0.01),而B(niǎo)cl-2蛋白陽(yáng)性表達(dá)則高于模型組(P0.05)。 5、模型組大鼠海馬凋亡細(xì)胞較正常組多(P0.01);舒郁寧心湯高、中、低劑量組和氟西汀組海馬凋亡細(xì)胞較模型組少(P0.01)。 【結(jié)論】動(dòng)物行為學(xué)結(jié)果顯示:舒郁寧心湯對(duì)抑郁模型大鼠有抗抑郁作用,其作用機(jī)制與提高抑郁模型大鼠海馬腦源性神經(jīng)營(yíng)養(yǎng)因子的含量,調(diào)節(jié)凋亡調(diào)控基因Bcl-2和Bax來(lái)減少海馬神經(jīng)元細(xì)胞凋亡有關(guān)。
[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.
【學(xué)位授予單位】:中國(guó)人民解放軍醫(yī)學(xué)院
【學(xué)位級(jí)別】:碩士
【學(xué)位授予年份】:2012
【分類號(hào)】:R285.5;R749.4
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