抑郁症模型大鼠HPA轴功能变化及柴胡疏肝散作用机理研究

发布时间：2018-05-20 10:51

本文选题：抑郁症 + 肝气郁结证　；参考：《河南中医学院》2014年硕士论文

【摘要】：[目的]观察抑郁症模型大鼠下丘脑-垂体-肾上腺（HPA）轴的功能变化及柴胡疏肝散对其的影响，探索抑郁症的发病机理及抑郁症中医肝气郁结证型与HPA轴功能紊乱是否具有相关性，进一步探究本病的证治机理。 [方法]大鼠喂养与造模：将45只健康的雄性SD大鼠，随机分为正常对照组、抑郁模型组及柴胡疏肝散组3组，每组15只；除正常对照组之外，其余两组大鼠给予21天的轻度慢性不可预见性应激刺激进行造模，柴胡疏肝散组大鼠从造模开始便每天给予中药灌胃，正常对照组与抑郁模型组的大鼠都给予相同剂量的0.9%NaCl灌胃。指标观测：造模期间每周给予体重的称量和OFT行为学的评定；光镜观察各组大鼠海马、下丘脑、垂体以及肾上腺皮质组织形态的病理学改变；Western blot法检测各组大鼠海马糖皮质激素受体（GR）和盐皮质激素受体（MR）及下丘脑促肾上腺皮质激素释放素（CRH）蛋白表达；Elisa法检测各组大鼠血浆促肾上腺皮质激素（ACTH）含量和血清皮质醇（CORT）含量。 [结果]1、造模3周后抑郁模型组大鼠多数出现精神萎靡，四肢活动减少，兴趣缺乏，体重减轻，OFT行为学水平运动得分与垂直运动得分均明显低于正常对照组（P0.05），提示抑郁模型大鼠造模成功；与抑郁模型组相比，柴胡疏肝散能增加抑郁模型大鼠体重和OFT行为学得分；2、与正常对照组相比较，抑郁模型组大鼠出现海马、下丘脑、垂体及肾上腺组织细胞形态损伤；与抑郁模型组相比较，柴胡疏肝散组大鼠在以上组织存在较轻的细胞形态损伤；3、与正常对照组相比，抑郁模型组大鼠海马GR蛋白表达明显降低（P0.05），下丘脑CRH表达显著升高（P0.05），血浆ACTH和血清CORT含量显著升高（P0.05）；与抑郁模型组相比，柴胡疏肝散组大鼠海马GR蛋白表达明显增高（P0.05），下丘脑CRH表达明显降低（P0.05），血浆ACTH和血清CORT含量显著下降（P0.05）；各组间大鼠海马MR的蛋白表达无明显差异。 [结论]1、抑郁模型大鼠海马、下丘脑等组织出现细胞形态损伤，柴胡疏肝散能改善损伤的组织细胞形态；2、抑郁模型大鼠存在HPA轴功能亢进，提示抑郁症的发生发展与HPA轴功能亢进密切相关，柴胡疏肝散能够有效的改善模型动物的抑郁症状；3、柴胡疏肝散通过增强海马GR蛋白的表达，进而调节下丘脑CRH蛋白的表达、降低血浆ACTH含量和血清CORT含量，，可能是其抗抑郁作用的机理之一；4、以方测证，柴胡疏肝散对抑郁症模型大鼠干预有效，初步验证肝气郁结证与HPA轴功能亢进有一定相关性。
[Abstract]:[objective] to observe the functional changes of hypothalamus-pituitary-adrenal (HPA) axis in rats with depression and the effect of Chaihu Shugan Powder on it. To explore the pathogenesis of depression and the relationship between the syndrome of stagnation of liver qi in depression and the dysfunction of HPA axis, and to further explore the mechanism of syndrome and treatment of this disease. [methods] Rat feeding and modeling: 45 healthy male SD rats were randomly divided into normal control group, depression model group and chaihu Shugan powder group with 15 rats in each group, except the normal control group. The other two groups were treated with mild chronic unpredictable stress stimulation for 21 days. The rats in the chaihu Shugan powder group were given Chinese medicine daily from the beginning of the model making. Rats in the normal control group and the depression model group were given the same dose of 0.9%NaCl. Index observation: weight weighing and OFT behavioral evaluation were given weekly during the modeling period, and the hippocampus and hypothalamus were observed under light microscope. Histopathological changes of pituitary and adrenocortical tissues: Western blot assay for the expression of glucocorticoid receptor (GRG), halocorticoid receptor (MRR) and hypothalamic adrenocorticotropin releasing hormone (CRH) protein in the hippocampus of rats in each group The content of ACTH in plasma and Cort in serum were measured. [results] 1. After 3 weeks of modeling, most of the rats in the depressive model group showed mental retardation, decreased limb activity and lack of interest. The scores of OFT behavioral level exercise and vertical exercise were significantly lower than those of the normal control group (P 0.05), which indicated that the depression model rats were successful in making the model, and compared with the depression model group, the OFT scores were significantly lower than those in the normal control group. Chaihu Shugan Powder could increase the body weight and OFT behavioral score of the depression model rats. Compared with the normal control group, the depression model rats had histopathologic damage of hippocampus, hypothalamus, pituitary and adrenal gland, and compared with the depression model group, the depressive model rats had the morphological damage of hippocampus, hypothalamus, pituitary and adrenal gland. Compared with the normal control group, Chaihu Shugan Powder group had slight cell morphological damage in the above tissues. In the depression model group, the expression of gr protein in hippocampus decreased significantly, the expression of CRH in hypothalamus increased significantly, and the content of plasma ACTH and serum CORT increased significantly in the depression model group, which was significantly higher than that in the depression model group. The expression of rat hippocampal gr protein was significantly increased in the chaihu Shugan powder group, the expression of CRH in hypothalamus decreased significantly, and the content of plasma ACTH and serum CORT decreased significantly, but there was no significant difference in the expression of Mr protein in hippocampus between each group. [conclusion] 1. In the depressive model rats, there were cellular morphological damage in hippocampus and hypothalamus, and Chaihu Shugan Powder could improve the injured tissue morphology. There was hyperfunction of HPA axis in the depression model rats. It is suggested that the occurrence and development of depression is closely related to the hyperfunction of HPA axis. Chaihu Shugan Powder can effectively improve the depression symptoms of model animals. Chaihu Shugan Powder can regulate the expression of CRH protein in hypothalamus by enhancing the expression of gr protein in hippocampus. The decrease of plasma ACTH content and serum CORT content may be one of the mechanisms of its antidepressant effect. According to the formula, Chaihu Shugan Powder is effective in intervention of depression model rats. It is preliminarily verified that the stagnation of liver-qi syndrome has certain correlation with hyperfunction of HPA axis.
【学位授予单位】：河南中医学院
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R-332;R285.5

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