异常黑胆质成熟剂抗抑郁作用的神经内分泌机制研究

发布时间：2019-01-23 16:49

【摘要】：目的：观察异常黑胆质成熟剂（简称异黑成熟颗粒，ASMq）对抑郁症大鼠下丘脑-垂体-肾上腺轴（HPA）组织形态学的影响，并通过检测抑郁症大鼠血清神经内分泌递质含量，探讨ASMq抗抑郁作用的神经内分泌机制。方法：采用慢性不可预见性温和应激（CUMs）诱导建立大鼠抑郁症模型，并用ASMq低、中、高剂量（1.5、3.0、6.0g/kg.BW）及氟西汀按（3.5mg/kg）对抑郁症模型进行全程干预，观察每组实验动物的生物表征、HPA轴组织形态学变化及血清促肾上腺皮质激素（ACTH）、皮质醇（CORT）、β-内啡肽（β-EP）、脑源性神经营养因子（BDNF）、去甲肾上腺素（NE）、多巴胺（DA）、5-羟色胺（5-HT）等神经内分泌递质含量变化。结果：与正常对照组比较，抑郁症模型组出现体形消瘦，毛发乱、无光泽和枯燥，烦躁不安，敏感性降低，体质量增长缓慢等生物表征；与抑郁症模型组相比，ASMq三个剂量组及阳性对照组大鼠体重增长缓慢（P0.05），毛发乱无光泽、枯燥、烦躁不安，敏感性降低等生物表征变化均得以改善。与正常对照组相比，，抑郁症模型组下丘脑星形胶质细胞水肿、增殖，内质网扩张，线粒体水肿，核轴系增宽；垂体远侧位细胞分布不均匀，显色细胞数量减少，细胞增殖，分泌颗粒减少，核仁边集，线粒体肿胀成空泡；肾上腺皮质水肿，细胞异形，线粒体水肿，核轴系增宽，核基质变淡等形态学改变；与抑郁症模型组相比，ASMq低、中剂量及阳性对照组大鼠下丘脑细胞水肿、增殖，线粒体水肿；垂体细胞增殖，分泌颗粒减少，核仁边集；肾上腺皮质水肿，细胞异形，线粒体水肿等形态学变化明显改善。与正常对照组比较，抑郁症模型组血清NE、5-HT、DA、β-EP、BDNF含量降低（P0.05~0.01）；ACTH、CORT含量升高（P0.01）；与抑郁症模型组相比，ASMq低、中剂量及阳性对照组大鼠血清ACTH含量明显降低（P0.05）；ASMq三个剂量及阳性对照组大鼠血清CORT含量都明显降低（P0.05），β-EP含量明显升高（P0.05），5-HT、DA含量明显升高（P0.01）；ASMq中、高剂量及阳性对照组大鼠血清BDNF含量明显升高（P0.05）；ASMq低、高剂量组大鼠血清NE含量明显升高（P0.05）。结论：ASMq对抑郁症模型动物HPA轴具有保护和修复功能，并降低抑郁症模型动物血清ACTH、CORT含量，增加血清BDNF、β-EP及单胺类神经递质含量，通过纠正HPA轴功能发挥抗抑郁作用。
[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.
【学位授予单位】：新疆医科大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R749.4

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