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異常黑膽質(zhì)成熟劑抗抑郁作用的神經(jīng)內(nèi)分泌機(jī)制研究

發(fā)布時(shí)間:2019-01-23 16:49
【摘要】:目的:觀察異常黑膽質(zhì)成熟劑(簡稱異黑成熟顆粒,ASMq)對抑郁癥大鼠下丘腦-垂體-腎上腺軸(HPA)組織形態(tài)學(xué)的影響,并通過檢測抑郁癥大鼠血清神經(jīng)內(nèi)分泌遞質(zhì)含量,探討ASMq抗抑郁作用的神經(jīng)內(nèi)分泌機(jī)制。方法:采用慢性不可預(yù)見性溫和應(yīng)激(CUMs)誘導(dǎo)建立大鼠抑郁癥模型,并用ASMq低、中、高劑量(1.5、3.0、6.0g/kg.BW)及氟西汀按(3.5mg/kg)對抑郁癥模型進(jìn)行全程干預(yù),觀察每組實(shí)驗(yàn)動物的生物表征、HPA軸組織形態(tài)學(xué)變化及血清促腎上腺皮質(zhì)激素(ACTH)、皮質(zhì)醇(CORT)、β-內(nèi)啡肽(β-EP)、腦源性神經(jīng)營養(yǎng)因子(BDNF)、去甲腎上腺素(NE)、多巴胺(DA)、5-羥色胺(5-HT)等神經(jīng)內(nèi)分泌遞質(zhì)含量變化。結(jié)果:與正常對照組比較,抑郁癥模型組出現(xiàn)體形消瘦,毛發(fā)亂、無光澤和枯燥,煩躁不安,敏感性降低,體質(zhì)量增長緩慢等生物表征;與抑郁癥模型組相比,ASMq三個劑量組及陽性對照組大鼠體重增長緩慢(P0.05),毛發(fā)亂無光澤、枯燥、煩躁不安,敏感性降低等生物表征變化均得以改善。與正常對照組相比,,抑郁癥模型組下丘腦星形膠質(zhì)細(xì)胞水腫、增殖,內(nèi)質(zhì)網(wǎng)擴(kuò)張,線粒體水腫,核軸系增寬;垂體遠(yuǎn)側(cè)位細(xì)胞分布不均勻,顯色細(xì)胞數(shù)量減少,細(xì)胞增殖,分泌顆粒減少,核仁邊集,線粒體腫脹成空泡;腎上腺皮質(zhì)水腫,細(xì)胞異形,線粒體水腫,核軸系增寬,核基質(zhì)變淡等形態(tài)學(xué)改變;與抑郁癥模型組相比,ASMq低、中劑量及陽性對照組大鼠下丘腦細(xì)胞水腫、增殖,線粒體水腫;垂體細(xì)胞增殖,分泌顆粒減少,核仁邊集;腎上腺皮質(zhì)水腫,細(xì)胞異形,線粒體水腫等形態(tài)學(xué)變化明顯改善。與正常對照組比較,抑郁癥模型組血清NE、5-HT、DA、β-EP、BDNF含量降低(P0.05~0.01);ACTH、CORT含量升高(P0.01);與抑郁癥模型組相比,ASMq低、中劑量及陽性對照組大鼠血清ACTH含量明顯降低(P0.05);ASMq三個劑量及陽性對照組大鼠血清CORT含量都明顯降低(P0.05),β-EP含量明顯升高(P0.05),5-HT、DA含量明顯升高(P0.01);ASMq中、高劑量及陽性對照組大鼠血清BDNF含量明顯升高(P0.05);ASMq低、高劑量組大鼠血清NE含量明顯升高(P0.05)。結(jié)論:ASMq對抑郁癥模型動物HPA軸具有保護(hù)和修復(fù)功能,并降低抑郁癥模型動物血清ACTH、CORT含量,增加血清BDNF、β-EP及單胺類神經(jīng)遞質(zhì)含量,通過糾正HPA軸功能發(fā)揮抗抑郁作用。
[Abstract]:Objective: to observe the effect of abnormal black bile maturation granule (, ASMq) on the histomorphology of hypothalamus-pituitary-adrenal axis (HPA) in depression rats, and to detect the content of neuroendocrine transmitters in serum of depressed rats. To explore the neuroendocrine mechanism of antidepressant effect of ASMq. Methods: the rat model of depression was induced by chronic unpredictable mild stress (CUMs) and ASMq was low and moderate. High dose (1.5 ~ 3.0g / kg 路BW) and fluoxetine (3.5mg/kg) were used in the whole course of intervention to observe the biological characteristics of each group of experimental animals. Histomorphologic changes of HPA axis and serum adrenocorticotropic hormone (ACTH), (CORT), 尾 -endorphin (尾 -EP), brain-derived neurotrophic factor (BDNF), noradrenaline (NE), dopamine (DA),) Changes of neuroendocrine transmitters such as 5-hydroxytryptamine (5-HT). Results: compared with the normal control group, the depression model group showed the biological signs of wasting, hair disorder, dull and dull, fidgety, low sensitivity and slow growth of body mass. Compared with the depression model group, the body weight of the three dose groups of ASMq and the positive control group increased slowly (P0.05), the hair was dull, fidgety, the sensitivity decreased and so on. Compared with normal control group, hypothalamic astrocyte edema, proliferation, endoplasmic reticulum dilatation, mitochondria edema and nuclear axis enlargement were observed in depression model group. The distribution of the distal pituitary cells was uneven, the number of chromogenic cells decreased, the cells proliferated, the secretory granules decreased, the nucleolar margins gathered, the mitochondria swelled into vacuoles. Morphological changes such as adrenal cortical edema, cell dysplasia, mitochondrial edema, nuclear axis widening, nuclear matrix thinning, etc. Compared with the depression model group, the hypothalamic cell edema, proliferation, mitochondria edema, pituitary cell proliferation, secretory granules and nucleolar side aggregation were lower in ASMq, middle dose and positive control group. Morphological changes such as adrenal cortical edema, cell dysplasia and mitochondrial edema were significantly improved. Compared with the normal control group, the serum NE,5-HT,DA, 尾-EP,BDNF level in the depression model group was decreased (P0.05 ~ 0. 01), the ACTH,CORT content was increased (P0. 01). Compared with the depression model group, ASMq was lower, and the content of serum ACTH in the middle dose and positive control group was significantly lower than that in the depression model group (P0.05). The contents of serum CORT, 尾-EP and 5-HTTDA were significantly decreased (P0.05), and the contents of 5-HTTDA were significantly increased (P0.01) in the three doses of ASMq and the positive control group (P0.05). In ASMq, the content of serum BDNF in the high dose group and the positive control group was significantly higher (P0.05); ASMq was lower, the serum NE level in the high dose group was significantly higher (P0.05). Conclusion: ASMq can protect and repair the HPA axis of depression model animals, decrease the content of serum ACTH,CORT, increase the contents of serum BDNF, 尾-EP and monoamine neurotransmitters. The antidepressant effect is played by correcting the function of HPA axis.
【學(xué)位授予單位】:新疆醫(yī)科大學(xué)
【學(xué)位級別】:碩士
【學(xué)位授予年份】:2012
【分類號】:R749.4

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