本文選題：抑郁癥 + 肝氣郁結(jié)證��； 參考：《河南中醫(yī)學(xué)院》2014年碩士論文

【摘要】：[目的]觀察抑郁癥模型大鼠下丘腦-垂體-腎上腺（HPA）軸的功能變化及柴胡疏肝散對(duì)其的影響，探索抑郁癥的發(fā)病機(jī)理及抑郁癥中醫(yī)肝氣郁結(jié)證型與HPA軸功能紊亂是否具有相關(guān)性，進(jìn)一步探究本病的證治機(jī)理。 [方法]大鼠喂養(yǎng)與造模：將45只健康的雄性SD大鼠，隨機(jī)分為正常對(duì)照組、抑郁模型組及柴胡疏肝散組3組，每組15只；除正常對(duì)照組之外，其余兩組大鼠給予21天的輕度慢性不可預(yù)見(jiàn)性應(yīng)激刺激進(jìn)行造模，柴胡疏肝散組大鼠從造模開(kāi)始便每天給予中藥灌胃，正常對(duì)照組與抑郁模型組的大鼠都給予相同劑量的0.9%NaCl灌胃。指標(biāo)觀測(cè)：造模期間每周給予體重的稱量和OFT行為學(xué)的評(píng)定；光鏡觀察各組大鼠海馬、下丘腦、垂體以及腎上腺皮質(zhì)組織形態(tài)的病理學(xué)改變；Western blot法檢測(cè)各組大鼠海馬糖皮質(zhì)激素受體（GR）和鹽皮質(zhì)激素受體（MR）及下丘腦促腎上腺皮質(zhì)激素釋放素（CRH）蛋白表達(dá)；Elisa法檢測(cè)各組大鼠血漿促腎上腺皮質(zhì)激素（ACTH）含量和血清皮質(zhì)醇（CORT）含量。 [結(jié)果]1、造模3周后抑郁模型組大鼠多數(shù)出現(xiàn)精神萎靡，四肢活動(dòng)減少，興趣缺乏，體重減輕，OFT行為學(xué)水平運(yùn)動(dòng)得分與垂直運(yùn)動(dòng)得分均明顯低于正常對(duì)照組（P0.05），提示抑郁模型大鼠造模成功；與抑郁模型組相比，柴胡疏肝散能增加抑郁模型大鼠體重和OFT行為學(xué)得分；2、與正常對(duì)照組相比較，抑郁模型組大鼠出現(xiàn)海馬、下丘腦、垂體及腎上腺組織細(xì)胞形態(tài)損傷；與抑郁模型組相比較，柴胡疏肝散組大鼠在以上組織存在較輕的細(xì)胞形態(tài)損傷；3、與正常對(duì)照組相比，抑郁模型組大鼠海馬GR蛋白表達(dá)明顯降低（P0.05），下丘腦CRH表達(dá)顯著升高（P0.05），血漿ACTH和血清CORT含量顯著升高（P0.05）；與抑郁模型組相比，柴胡疏肝散組大鼠海馬GR蛋白表達(dá)明顯增高（P0.05），下丘腦CRH表達(dá)明顯降低（P0.05），血漿ACTH和血清CORT含量顯著下降（P0.05）；各組間大鼠海馬MR的蛋白表達(dá)無(wú)明顯差異。 [結(jié)論]1、抑郁模型大鼠海馬、下丘腦等組織出現(xiàn)細(xì)胞形態(tài)損傷，柴胡疏肝散能改善損傷的組織細(xì)胞形態(tài)；2、抑郁模型大鼠存在HPA軸功能亢進(jìn)，提示抑郁癥的發(fā)生發(fā)展與HPA軸功能亢進(jìn)密切相關(guān)，柴胡疏肝散能夠有效的改善模型動(dòng)物的抑郁癥狀；3、柴胡疏肝散通過(guò)增強(qiáng)海馬GR蛋白的表達(dá)，進(jìn)而調(diào)節(jié)下丘腦CRH蛋白的表達(dá)、降低血漿ACTH含量和血清CORT含量，，可能是其抗抑郁作用的機(jī)理之一；4、以方測(cè)證，柴胡疏肝散對(duì)抑郁癥模型大鼠干預(yù)有效，初步驗(yàn)證肝氣郁結(jié)證與HPA軸功能亢進(jìn)有一定相關(guān)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.
【學(xué)位授予單位】：河南中醫(yī)學(xué)院
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類號(hào)】：R-332;R285.5

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