逍遥舒心胶囊抗抑郁作用及机制研究
发布时间：2018-08-25 15:35
【摘要】：目的通过建立慢性不可预见应激(CUMS)加孤养小鼠模型,观察逍遥舒心胶囊抗抑郁作用,探讨逍遥舒心胶囊抗抑郁作用机制,为临床用药提供实验依据。 方法①逍遥舒心胶囊抗抑郁作用实验研究：ICR小鼠60只,雌雄各半,随机分为空白对照、模型对照、逍遥丸(1.5g/kg)阳性对照、逍遥舒心胶囊低(0.5g/kg)、中(1.5g/kg)、高(4.5g/kg)剂量组,每组10只,除空白组常规饲养外,其余各组采用慢性不可预见应激加孤养法复制抑郁症模型,并于造模第1d开始以20ml/kg灌胃给药,每日一次,连续5周,空白组和模型组给予等量生理盐水。全程观察各组小鼠一般形态情况；在第0、14、21、28、35d观察各组小鼠体重与摄食情况；在第0、21、35d观察各组小鼠糖水偏好度情况；末次给药后,对各组小鼠进行悬尾实验、强迫游泳实验、开阔场实验、自主活动实验等抑郁症相关实验检测。②逍遥舒心胶囊抗抑郁作用机制实验研究：上述行为学指标考察结束后,各组小鼠从腹主动脉取血,取血结束后迅速断头取出脑组织,将所得血液和脑组织制成血清和脑组织匀浆,采用酶联免疫吸附(ELISA)法测定脑组织匀浆中5-羟色胺(5-HT)、促肾上腺皮质激素(ACTH)以及脑源性神经营养因子(BDNF)含量；采用分光光度法测定血清中超氧化物歧化酶(SOD)活力以及丙二醛(MDA)含量。 结果①逍遥舒心胶囊抗抑郁作用：显著改善抑郁症模型小鼠一般形态；提高抑郁症模型小鼠摄食量,加快体重增长速度,改善消瘦、食欲减退等抑郁症症状；显著提高抑郁症模型小鼠糖水偏好度,改善快感缺失的抑郁症症状；显著降低抑郁症模型小鼠悬尾不动和强迫游泳停滞时间,减少悲观绝望情绪；提高抑郁症模型小鼠爬行总格数和自主活动次数,降低中央格停留时间,提高抑郁症小鼠在新鲜环境的探索能力、兴奋性和活动能力。②逍遥舒心胶囊抗抑郁作用机制：显著升高抑郁症模型小鼠脑组织中5-HT.BDNF含量；显著降低抑郁症模型小鼠脑组织中ACTH含量；显著升高抑郁症模型小鼠血清中SOD活力,降低MDA含量。 结论逍遥舒心胶囊对慢性不可预见应激加孤养法抑郁症小鼠模型具有显著的治疗作用,可全面、有效改善抑郁症小鼠模型抑郁症状。其作用机制可能与提高脑组织中单胺类神经递质功能,改善下丘脑-垂体-肾上腺(HPA)轴功能紊乱,提高神经可塑性、促进神经发生及改善机体自由基损伤等多种途径有关。
[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.
【学位授予单位】：浙江中医药大学
【学位级别】：硕士
【学位授予年份】：2013
【分类号】：R285.5;R749.4
本文编号：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.
【学位授予单位】：浙江中医药大学
【学位级别】：硕士
【学位授予年份】：2013
【分类号】：R285.5;R749.4
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