逍遙舒心膠囊抗抑郁作用及機(jī)制研究
發(fā)布時(shí)間：2018-08-25 15:35
【摘要】：目的通過(guò)建立慢性不可預(yù)見(jiàn)應(yīng)激(CUMS)加孤養(yǎng)小鼠模型,觀察逍遙舒心膠囊抗抑郁作用,探討逍遙舒心膠囊抗抑郁作用機(jī)制,為臨床用藥提供實(shí)驗(yàn)依據(jù)。 方法①逍遙舒心膠囊抗抑郁作用實(shí)驗(yàn)研究：ICR小鼠60只,雌雄各半,隨機(jī)分為空白對(duì)照、模型對(duì)照、逍遙丸(1.5g/kg)陽(yáng)性對(duì)照、逍遙舒心膠囊低(0.5g/kg)、中(1.5g/kg)、高(4.5g/kg)劑量組,每組10只,除空白組常規(guī)飼養(yǎng)外,其余各組采用慢性不可預(yù)見(jiàn)應(yīng)激加孤養(yǎng)法復(fù)制抑郁癥模型,并于造模第1d開(kāi)始以20ml/kg灌胃給藥,每日一次,連續(xù)5周,空白組和模型組給予等量生理鹽水。全程觀察各組小鼠一般形態(tài)情況；在第0、14、21、28、35d觀察各組小鼠體重與攝食情況；在第0、21、35d觀察各組小鼠糖水偏好度情況；末次給藥后,對(duì)各組小鼠進(jìn)行懸尾實(shí)驗(yàn)、強(qiáng)迫游泳實(shí)驗(yàn)、開(kāi)闊場(chǎng)實(shí)驗(yàn)、自主活動(dòng)實(shí)驗(yàn)等抑郁癥相關(guān)實(shí)驗(yàn)檢測(cè)。②逍遙舒心膠囊抗抑郁作用機(jī)制實(shí)驗(yàn)研究：上述行為學(xué)指標(biāo)考察結(jié)束后,各組小鼠從腹主動(dòng)脈取血,取血結(jié)束后迅速斷頭取出腦組織,將所得血液和腦組織制成血清和腦組織勻漿,采用酶聯(lián)免疫吸附(ELISA)法測(cè)定腦組織勻漿中5-羥色胺(5-HT)、促腎上腺皮質(zhì)激素(ACTH)以及腦源性神經(jīng)營(yíng)養(yǎng)因子(BDNF)含量；采用分光光度法測(cè)定血清中超氧化物歧化酶(SOD)活力以及丙二醛(MDA)含量。 結(jié)果①逍遙舒心膠囊抗抑郁作用：顯著改善抑郁癥模型小鼠一般形態(tài)；提高抑郁癥模型小鼠攝食量,加快體重增長(zhǎng)速度,改善消瘦、食欲減退等抑郁癥癥狀；顯著提高抑郁癥模型小鼠糖水偏好度,改善快感缺失的抑郁癥癥狀；顯著降低抑郁癥模型小鼠懸尾不動(dòng)和強(qiáng)迫游泳停滯時(shí)間,減少悲觀絕望情緒；提高抑郁癥模型小鼠爬行總格數(shù)和自主活動(dòng)次數(shù),降低中央格停留時(shí)間,提高抑郁癥小鼠在新鮮環(huán)境的探索能力、興奮性和活動(dòng)能力。②逍遙舒心膠囊抗抑郁作用機(jī)制：顯著升高抑郁癥模型小鼠腦組織中5-HT.BDNF含量；顯著降低抑郁癥模型小鼠腦組織中ACTH含量；顯著升高抑郁癥模型小鼠血清中SOD活力,降低MDA含量。 結(jié)論逍遙舒心膠囊對(duì)慢性不可預(yù)見(jiàn)應(yīng)激加孤養(yǎng)法抑郁癥小鼠模型具有顯著的治療作用,可全面、有效改善抑郁癥小鼠模型抑郁癥狀。其作用機(jī)制可能與提高腦組織中單胺類神經(jīng)遞質(zhì)功能,改善下丘腦-垂體-腎上腺(HPA)軸功能紊亂,提高神經(jīng)可塑性、促進(jìn)神經(jīng)發(fā)生及改善機(jī)體自由基損傷等多種途徑有關(guān)。
[Abstract]:Objective to observe the antidepressant effect of Xiaoyao Shuxin capsule (XXC) and explore the antidepressant mechanism of Xiaoyaoshuxin capsule (XXC) by establishing the model of chronic unpredictable stress (CUMS) combined with solitary rearing mice to provide experimental evidence for clinical use of drugs. Methods 1Experimental study on antidepressant effect of Xiaoyaoshuxin capsule in 60 mice, half male and half female, was randomly divided into blank control, model control, 1.5g/kg positive control, Xiaoyaoshuxin capsule low (0.5g/kg), middle (1.5g/kg) and high (4.5g/kg) dosage groups (10 rats in each group). Except for the blank group, the depression model was induced by chronic unpredictable stress and solitary nourishment. The depression model was treated with 20ml/kg once a day for 5 weeks on the 1st day. The blank group and the model group were given the same amount of normal saline. Observe the general morphology of the mice in the whole course; observe the body weight and food intake of the mice in each group on the 35th day; observe the preference degree of sugar water for the mice in each group on the day 011,35; after the last administration of the drug, do the tail suspension test and the forced swimming test on the mice in each group. Experimental study on the antidepressant mechanism of Xiaoyao Shuxin capsule in depression related experiments such as open field experiment, autonomous activity test and so on: after the above behavioral indexes were investigated, blood was taken from abdominal aorta in each group. After the blood was taken out, the brain tissue was quickly cut off, and the blood and brain tissue were made into serum and brain homogenate. The contents of 5-hydroxytryptamine (5-HT), adrenocorticotropic hormone (ACTH) and brain-derived neurotrophic factor (BDNF) in brain homogenate were determined by enzyme-linked immunosorbent assay (ELISA). The activity of superoxide dismutase (SOD) and the content of malondialdehyde (MDA) in serum were determined by spectrophotometry. Results (1) the antidepressant effect of XiaoyaoShuxin capsule: significantly improved the general morphology of the depression model mice, increased the food intake, accelerated the weight growth rate, improved the depression symptoms such as loss of weight, loss of appetite and so on; The sugar water preference degree of depression model mice was significantly increased, the depression symptom of lack of pleasure was ameliorated, the time of suspending tail immobility and forced swimming stagnation in depression model mice was significantly reduced, and the pessimism and despair were reduced. To increase the total number of crawling cells and the number of autonomous activities, to reduce the residence time of central lattice, and to improve the exploring ability of depression mice in fresh environment. The antidepressant mechanism of Xiaoyaoshuxin capsule: significantly increased the content of 5-HT.BDNF in the brain tissue of the depression model mice, significantly decreased the content of ACTH in the brain tissue of the depression model mice, and significantly decreased the content of ACTH in the brain tissue of the depression model mice. The activity of SOD in serum and the content of MDA in serum of depression model mice were significantly increased. Conclusion Xiaoyao Shuxin capsule has a significant therapeutic effect on chronic unpredictable stress and solitary nourishing depression mice model, and can effectively improve the depression symptoms of depression mice model. The mechanism may be related to the enhancement of monoamine neurotransmitter function in brain tissue, the improvement of hypothalamus-pituitary-adrenal (HPA) axis dysfunction, the enhancement of neural plasticity, the promotion of neurogenesis and the improvement of free radical injury.
【學(xué)位授予單位】：浙江中醫(yī)藥大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2013
【分類號(hào)】：R285.5;R749.4
本文編號(hào)：2203352
[Abstract]:Objective to observe the antidepressant effect of Xiaoyao Shuxin capsule (XXC) and explore the antidepressant mechanism of Xiaoyaoshuxin capsule (XXC) by establishing the model of chronic unpredictable stress (CUMS) combined with solitary rearing mice to provide experimental evidence for clinical use of drugs. Methods 1Experimental study on antidepressant effect of Xiaoyaoshuxin capsule in 60 mice, half male and half female, was randomly divided into blank control, model control, 1.5g/kg positive control, Xiaoyaoshuxin capsule low (0.5g/kg), middle (1.5g/kg) and high (4.5g/kg) dosage groups (10 rats in each group). Except for the blank group, the depression model was induced by chronic unpredictable stress and solitary nourishment. The depression model was treated with 20ml/kg once a day for 5 weeks on the 1st day. The blank group and the model group were given the same amount of normal saline. Observe the general morphology of the mice in the whole course; observe the body weight and food intake of the mice in each group on the 35th day; observe the preference degree of sugar water for the mice in each group on the day 011,35; after the last administration of the drug, do the tail suspension test and the forced swimming test on the mice in each group. Experimental study on the antidepressant mechanism of Xiaoyao Shuxin capsule in depression related experiments such as open field experiment, autonomous activity test and so on: after the above behavioral indexes were investigated, blood was taken from abdominal aorta in each group. After the blood was taken out, the brain tissue was quickly cut off, and the blood and brain tissue were made into serum and brain homogenate. The contents of 5-hydroxytryptamine (5-HT), adrenocorticotropic hormone (ACTH) and brain-derived neurotrophic factor (BDNF) in brain homogenate were determined by enzyme-linked immunosorbent assay (ELISA). The activity of superoxide dismutase (SOD) and the content of malondialdehyde (MDA) in serum were determined by spectrophotometry. Results (1) the antidepressant effect of XiaoyaoShuxin capsule: significantly improved the general morphology of the depression model mice, increased the food intake, accelerated the weight growth rate, improved the depression symptoms such as loss of weight, loss of appetite and so on; The sugar water preference degree of depression model mice was significantly increased, the depression symptom of lack of pleasure was ameliorated, the time of suspending tail immobility and forced swimming stagnation in depression model mice was significantly reduced, and the pessimism and despair were reduced. To increase the total number of crawling cells and the number of autonomous activities, to reduce the residence time of central lattice, and to improve the exploring ability of depression mice in fresh environment. The antidepressant mechanism of Xiaoyaoshuxin capsule: significantly increased the content of 5-HT.BDNF in the brain tissue of the depression model mice, significantly decreased the content of ACTH in the brain tissue of the depression model mice, and significantly decreased the content of ACTH in the brain tissue of the depression model mice. The activity of SOD in serum and the content of MDA in serum of depression model mice were significantly increased. Conclusion Xiaoyao Shuxin capsule has a significant therapeutic effect on chronic unpredictable stress and solitary nourishing depression mice model, and can effectively improve the depression symptoms of depression mice model. The mechanism may be related to the enhancement of monoamine neurotransmitter function in brain tissue, the improvement of hypothalamus-pituitary-adrenal (HPA) axis dysfunction, the enhancement of neural plasticity, the promotion of neurogenesis and the improvement of free radical injury.
【學(xué)位授予單位】：浙江中醫(yī)藥大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2013
【分類號(hào)】：R285.5;R749.4
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