疏肝、健脾、疏肝健脾方对肝郁脾虚证模型动物外观表征及行为学的影响
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摘要
方剂是由多味中药配伍而成、具有特定功用和主治的一种防疾治病的工具。其配伍与其所主病证病机或病理环节之间具有高度的相关性或针对性,即“方证相关”。通常针对一个特定病证可能会有数个方剂起作用,但疗效存在差异,或同一方剂作用于不同病证会呈现不同的治疗效果。“方证相关”是中医辨证论治原理的核心,也是方剂学学理的重要逻辑基础。研究方与证之间的关系对揭示辨证论治原理具有重要的理论与实践意义。
本课题采用慢性束缚+饮食失节+过度疲劳法复制出肝郁脾虚证动物模型,以模型动物外观行为作切入点,比较观察具有疏肝、健脾、疏肝健脾不同功效的柴胡疏肝散、四君子汤、柴疏四君汤对模型大鼠外观行为变化作用的异同,并探查模型的中枢递质及生化物的变化和三方对其变化的影响。
论文包括文献综述和实验研究两部分。文献综述对肝郁脾虚证及柴胡疏肝散、四君子汤、柴疏四君汤三方的临床与实验研究概况进行了综述。实验研究观察了肝郁脾虚证大鼠模型外观行为表征及其中枢神经递质及有关生化物的变化和柴胡疏肝散、四君子汤、柴疏四君汤三方对该模型的相关作用。
研究方法：将大鼠随机分为正常对照组、肝郁脾虚模型组(以下简称模型组)、柴疏四君汤组、四君子汤组、柴胡疏肝散组共5组,每组12只。后4组大鼠于每天8：00 am置于束缚器中限制3h,2：00pm置于盛有温水(22±1℃)的大塑料桶中游泳10 min,隔日喂食(隔日禁食,隔日足量给食),连续4周；正常对照组不施加任何刺激,自然饲养。于造模第15天,中药各组大鼠分别给予柴疏四君汤4.27g／kg、四君子汤4.53g／kg、柴胡疏肝散4.2g／kg灌胃,每天1次；模型组与对照组分别给予等量蒸馏水,连续14天。并于第7d、14d、21d、28d,分早、中、晚三个时间点观察并记录各组大鼠的行为状态、活跃程度、情绪反应、皮肤毛发、饮食状态、睡眠状态、大便状态等方面的变化；于每周第7天2：00-2：30pm测定各组大鼠的体重；于第14d、28d通过旷场实验记录大鼠5min内爬行格数、直立次数、修饰时间及中央格停留时间。于第29天8：00am断头处死,在冰盘上迅速剥离大鼠海马、下丘脑和脑干,置于液氮罐中保存,待测。采用高效液相色谱荧光法测定海马组织中Asp、Glu、GABA、Gly、Tau;采用放射免疫法测定下丘脑组织中cAMP、PGE2;采用酶联免疫法测定脑干组织中P450酶的活性及含量。
统计学方法：所得数据均以χ±S表示,采用单因素方差分析(one-way ANOVA)进行检验后,多组间比较采用Student Newman Keuls Test检验。全部数据采用SPSS 13.0 for windows软件统计处理。
研究结果：1.肝郁脾虚证模型大鼠外观表征的变化及相关方药的作用：造模1周后,模型组、柴疏四君汤组、四君子汤组、柴胡疏肝散组大鼠行为活动、情绪反应、皮肤毛发、饮食、睡眠与大便状态等均未有明显变化。模型组大鼠造模2周后即表现出活动减少、活跃程度减弱、情绪易怒、饮食减少、皮毛不顺泽、易醒、便干等；造模3周后开始出现动作迟缓、情绪不稳、饮食减少、皮毛不泽、倦卧、便溏；造模4周后,则出现明显的活动减少、扎堆甚至倦卧多睡,情绪由开始的易激惹状态转为情绪低落、争斗减少,饮食减少,皮毛枯乱,大便稀溏等。与模型组比较,3个中药组大鼠在给药1周后(造模3周后),活动增加,情绪趋于稳定,饮食有增,皮毛、睡眠与大便状态均见不同程度好转。给药2周后(造模4周后),柴疏四君汤组大鼠行为活动明显增加、反应敏捷、皮毛接近顺整、饮食增加、睡眠深浅适度、大便成形；四君子汤组大鼠在皮毛、饮食、睡眠与大便状态改善方面明显；柴胡疏肝散组大鼠在行为状态、活跃程度、情绪反应等方面均见明显好转。
2.肝郁脾虚证模型大鼠体重的变化及相关方药的作用：实验期间,正常组大鼠体重明显增加,模型组与3个给药组大鼠体重增加较为缓慢,其中模型组、柴疏四君汤组和四君子汤组大鼠在第1周末体重出现负增长；模型组与柴胡疏肝散组大鼠在第4周末体重出现下降趋势。与正常组比较,模型组与柴疏四君汤组、四君子汤组、柴胡疏肝散组大鼠在第1w、2w、3w、4w末的体重均明显降低,差异具有显著性意义(P<0.05)。与模型组比较,3个给药组大鼠体重变化无显著性差异(P>0.05)；且3个给药组间大鼠体重变化无明显差异(P>0.05)。
3.肝郁脾虚证模型大鼠自主行为的变化及相关方药的作用：与正常组比较,造模第14天时的模型组与3个中药组大鼠的爬行格数明显增加,差异具有显著性意义(P<0.01或P<0.05)；模型组、柴疏四君汤组大鼠直立次数增加,差异具有显著性意义(P0.05)；模型组与四君子汤组大鼠直立次数增加,差异有显著性意义(P<0.05),柴疏四君汤组与柴胡疏肝散组大鼠增加不明显(P>0.05)；模型组与3个中药组大鼠修饰时间、中央格停留时间均有延长,但差异无显著性意义(P>0.05)。与模型组比较,3个中药组大鼠的爬行格数和直立次数均有不同程度的降低,其中柴疏四君汤组爬行格数降低明显,差异有显著性意义(P<0.05)
4.肝郁脾虚证模型大鼠中枢神经生化指标的变化及相关方药的作用：(1)与正常组比较,模型组大鼠海马组织中Asp(天冬氨酸)的含量呈升高趋势,Glu(谷氨酸)、GABA(Y-氨基丁酸)、Gly(甘氨酸)、Tau(牛磺酸)的含量呈下降趋势,但差异均无显著性意义(P>0.05)；下丘脑组织中PGE2和cAMP的变化均无显著性差异(P>0.05)；脑干P450酶活性与酶含量的变化均无显著性差异(P>0.05)。(2)与模型组比较,3个中药组大鼠的上述指标均无明显变化(P>0.05)。
研究结论：采用慢性束缚+饮食失节+过度疲劳法制备的肝郁脾虚证模型大鼠表现出活动减少、扎堆多睡、情绪低落、争斗减少、饮食减少,皮毛枯乱,大便稀溏、体重减轻等,同时伴有自主活动增强的行为特征。经柴疏四君汤、四君子汤、柴胡疏肝散治疗2周后,可使模型大鼠外观表征呈现不同程度的改善,并对自主活动具有一定调节作用,其中以柴疏四君汤的干预效果最佳,柴胡疏肝散和四君子汤在改善模型大鼠外观表征中的行为状态、情绪反应和皮肤毛发、睡眠状态等方面各有侧重。结果表明,该模型具有类似于肝郁脾虚证的中医证候的一些特点,柴疏四君汤与该证模型具有更高的关联性,符合“疏肝健脾与肝郁脾虚证相应”的中医证治经验。
本研究为肝郁脾虚证模型的中医证候学评价提供一定的研究思路,为理解“方证相关”的内涵及认识相关方剂的功用提供了一定的现代依据。
Prescription is a tool with a specific function and the main treatment for disease prevention, Which is made by a number of herbs compatibility. There is a a high degree of correlation or focused references between the compatibility their primary disease pathogenesis or pathological evidence. This is called "The correlation between formula and syndrome."Evidence for a specific disease may have a few formulas work, but the results are different, or the same role in different disease and syndrome prescriptions would be different treatment. "The correlation between formula and syndrome" is the core principle of traditional Chinese medicine dialectical thinking, but also to learn prescription based on the logic of justification. Study the relationship between the formula and the syndrome to reveal the syndrome differentiation theory has important theoretical and practical significance.
this study in rats with chronic astricting+diet+excess fatigue to replicate animal model of liver depression and spleen deficiency.To act as entry points from the appearance of animal model to compare the observations of rats'the appearance of behavioral change on the role of the differences and similarities, with the Liver, Spleen, Liver Spleen different effects of chaihushugansan. Sijunzitang and chaishusijuntang.And then and the ascertain the central neurotransmitters and biochemical changes of the model animal and and the changes result in the different formulae.
This dissertation contains of literature review and experimental research. Research evolutions of clinic and experiment about the model of stagnation of liver and deficiency of spleen (GYPX), chaihushugansan. Sijunzitang and chaishusijuntang are summed up.Experimental study observed stagnation and spleen deficiency syndrome in rats characterized by the appearance of behavior and central neurotransmitters and related biochemical changes in things and chaihushugansan. Sijunzitang and chaishusijuntang. relevant role of the models.
Methods:Rats were randomly divided into normal control group, liver depression and spleen deficiency syndrome group (hereafter referred to as the model group), chaishusijuntang groups,SiJunzi tang group and chaihushugansan group. Each group has 12 annimals. the latter 4 groups of rats were placed in restraint devices every day 8:00 am restriction of 3 h,2:00 pm place filled with warm water (22±1℃) swimming in a large plastic bucket 10 min, every other day feeding (every other day ban food, enough to eat every other day) for 4 weeks; normal control group did not exert any stimulating natural feeding. At 15 days of modeling, the rats were treated with traditional Chinese medicine Chaishusijun Tang 4.27g/kg, Sijuzitang 4.53g/kg, ChauhuShugan San 4.2g/kg orally,1 time per day; model group with the control group were given distilled water for 14 days. And in the first 7d,14d,21d,28d, points early, middle and later time points the rats were observed and recorded changes in the behavior of state, activity level, emotional reactions, skin hair, food intake, sleep, stool state, etc.; In the first 7 days a week 2:00-2:30 pm Determination of body weight of rats in each group; in the first 14d,28d by open field test rats were recorded within 5min crawling cell number, number of rearing, modification time and Time on the central grid.8:00 am on the 29th day were decapitated, rapidly stripping the Ice hippocampus, hypothalamus and brain stem, placed in liquid nitrogen tanks stored, tested. High Performance Liquid Chromatography and Fluorescence Detection hippocampus Asp, Glu, GABA, Gly, Tau; measured by radioimmunoassay in the hypothalamus of cAMP, PGE2; by enzyme-linked immunosorbent assay in the brain stem P450 enzyme activity and content.
Statistical Methods:The data were to described an x±S, After the single factor analysis of variance (one-way ANOVA) to test, the more groups were analyzed using Student Newman Keuls Test test. All data using SPSS 13.0 for windows statistical processing software.
Results:1. Syndrome Model of rats and related changes in appearance characterized the role of herbs:1 week after modeling, model group, chaishusijuntang group, SiJunzitang group, chaihushugansan group's behavioral activity, emotional reactions, skin hair, diet, sleep and defecate state all did not change. Model rats 2 weeks after modeling showed reduced activity, reduced the level of activity, mood irritability, food intake, fur ring true Chak, easy to wake up, then dry, etc.; 3 weeks after modeling,the model group began to slow down the movement, emotions stability, food intake, fur is not Chak, tired of lying, loose stools; 4 weeks after modeling, the significant reduction of activities, get together or even tired of lying to sleep, emotional state from the beginning of the irritability to depression, the struggle to reduce, food intake, coat dry mess, loose stool and so on. Compared with model group, the rats in the administration of Chinese medicine after 1 week (3 weeks after modeling), activity, mood stabilization, food has increased, fur, sleep and bowel movements were seen in varying degrees of improvement in the state. After 2 weeks of administration (4 weeks of modeling), chaishusijuntang group significantly increased behavioral activity, responsive, smooth fur close to the whole, food increased, the depth of sleep, moderate, formed stool;sijuzitang grope, the rats'fur, food, sleep and improvement of stool condition obviously; rats of chaihushugansan in behavioral state, activity level, emotional response and so on were see significant improvement.
2. Syndrome Model of body weight change and related prescriptions in Action: During the experiment, body weight of the normal rats was significantly increased,while the body weight in model group and three treated group gained weight more slowly, in which the model group, chaishusijuntang Group and sijunzitang group body weight had a negative growth in the first weekend. The weigh of the model group rats, chauhushugansan group showed a downward trend,after 4 weeks.Compared with normal group, the body weight of model group and chaishusijuntang group, SiJunzitang group, chaihushugansan group were significantly decreased at the end of 1w,2w,3w,4w. the difference was significant (P <0.05). Compared with model group, three treated group no significant changes in body weight difference (P> 0.05); and three dose groups no significant difference in body weight change (P> 0.05).
3. Syndrome Model of autonomous behavior in rats and related changes in the role of herbs:Compared with normal group, he number of crawling cells of model group and the three Chinese medicine groups significantly increased (P<0.01 or P <0.05) in the first 14 days of modeling, the difference; The rats of model group and chaishusijuntang vertical had increased, the difference was significant (P<0.05); model group, sijunzitang group modification time and the central grid residence time were extended, of which modifiede time'difference was significant (P<0.05). After 2 weeks of administration (At the 28th day), compared with the normal group, the number of rats crawling cells increased model group, sijunzitang group and chaishusijuntang group, the differences were significant (P<0.05), the number of rats crawling cells of chaishusijuntang close to the normal level (P> 0.05); The model group and sijunzitang group vertical increased in the number, the difference was significant (P<0.05), chaishusijuzitang group and chaihushugans group didn't increased obviously (P> 0.05); The modification time and time of he central cell residence of model group and three Chinese medicine group, were extended, but the difference was not significant (P> 0.05). Compared with model group, crawling cell number and were s number of rearing of 3 Chinese medicine groups significantly lower. the number of crawling cells of chaishusijuntang group reduced significantly, the difference was significant (P<0.05).
4. Syndrome Model of central nervous and related biochemical changes in the role of prescriptions:(1) Compared with with the normal group, hippocampus Asp (aspartic acid) of model group content tended to increase Glu (glutamic acid), GABA (y-aminobutyric acid), Gly (glycine), Tau (taurine) were decreased, but the differences were not significant (P> 0.05); PGE2 and cAMP in the hypothalamus changed not significantly different (P> 0.05); brainstem P450 enzyme activity and enzyme content in no significant difference (P> 0.05). (2) Compared with model group, three Chinese medicine group had no significant change in the above index (P> 0.05).
Conclusions:The chronic restraint+diet+excess fatigue Disloyalty prepared Syndrome Model of rats showed reduced activities, get together to sleep, depression, fighting less, eating less, fur dry mess, loose stool, weight loss and so on, accompanied by the enhanced spontaneous activity behavior.2 weeks after the treat with chaishusijuntang, sijunzitang, chaihushugansan, rats can characterize the appearance of varying degrees of improvements and self-regulate certain activities.Then intervention effct of chaihusijuntang group is best,chauhushugansan group and sijuzitang has had play respective role in the behavioral state,emotional reactions and the skin hair, sleep and so on. These results show that the model is similar to the stagnation and spleen deficiency syndromes in some features, chaishusijuntang and this model has a higher correlation, consistent with "Shuganjianpi corresponding spleen deficiency and stagnation" in TCM experience.
This study Syndrome Model of Syndrome Evaluation study provides some ideas for evaluating TCM Syndrome.lt also can provided some of modern basis for understanding the meaning"evidence related parties" and function of the relevant formulas.
本课题采用慢性束缚+饮食失节+过度疲劳法复制出肝郁脾虚证动物模型,以模型动物外观行为作切入点,比较观察具有疏肝、健脾、疏肝健脾不同功效的柴胡疏肝散、四君子汤、柴疏四君汤对模型大鼠外观行为变化作用的异同,并探查模型的中枢递质及生化物的变化和三方对其变化的影响。
论文包括文献综述和实验研究两部分。文献综述对肝郁脾虚证及柴胡疏肝散、四君子汤、柴疏四君汤三方的临床与实验研究概况进行了综述。实验研究观察了肝郁脾虚证大鼠模型外观行为表征及其中枢神经递质及有关生化物的变化和柴胡疏肝散、四君子汤、柴疏四君汤三方对该模型的相关作用。
研究方法：将大鼠随机分为正常对照组、肝郁脾虚模型组(以下简称模型组)、柴疏四君汤组、四君子汤组、柴胡疏肝散组共5组,每组12只。后4组大鼠于每天8：00 am置于束缚器中限制3h,2：00pm置于盛有温水(22±1℃)的大塑料桶中游泳10 min,隔日喂食(隔日禁食,隔日足量给食),连续4周；正常对照组不施加任何刺激,自然饲养。于造模第15天,中药各组大鼠分别给予柴疏四君汤4.27g／kg、四君子汤4.53g／kg、柴胡疏肝散4.2g／kg灌胃,每天1次；模型组与对照组分别给予等量蒸馏水,连续14天。并于第7d、14d、21d、28d,分早、中、晚三个时间点观察并记录各组大鼠的行为状态、活跃程度、情绪反应、皮肤毛发、饮食状态、睡眠状态、大便状态等方面的变化；于每周第7天2：00-2：30pm测定各组大鼠的体重；于第14d、28d通过旷场实验记录大鼠5min内爬行格数、直立次数、修饰时间及中央格停留时间。于第29天8：00am断头处死,在冰盘上迅速剥离大鼠海马、下丘脑和脑干,置于液氮罐中保存,待测。采用高效液相色谱荧光法测定海马组织中Asp、Glu、GABA、Gly、Tau;采用放射免疫法测定下丘脑组织中cAMP、PGE2;采用酶联免疫法测定脑干组织中P450酶的活性及含量。
统计学方法：所得数据均以χ±S表示,采用单因素方差分析(one-way ANOVA)进行检验后,多组间比较采用Student Newman Keuls Test检验。全部数据采用SPSS 13.0 for windows软件统计处理。
研究结果：1.肝郁脾虚证模型大鼠外观表征的变化及相关方药的作用：造模1周后,模型组、柴疏四君汤组、四君子汤组、柴胡疏肝散组大鼠行为活动、情绪反应、皮肤毛发、饮食、睡眠与大便状态等均未有明显变化。模型组大鼠造模2周后即表现出活动减少、活跃程度减弱、情绪易怒、饮食减少、皮毛不顺泽、易醒、便干等；造模3周后开始出现动作迟缓、情绪不稳、饮食减少、皮毛不泽、倦卧、便溏；造模4周后,则出现明显的活动减少、扎堆甚至倦卧多睡,情绪由开始的易激惹状态转为情绪低落、争斗减少,饮食减少,皮毛枯乱,大便稀溏等。与模型组比较,3个中药组大鼠在给药1周后(造模3周后),活动增加,情绪趋于稳定,饮食有增,皮毛、睡眠与大便状态均见不同程度好转。给药2周后(造模4周后),柴疏四君汤组大鼠行为活动明显增加、反应敏捷、皮毛接近顺整、饮食增加、睡眠深浅适度、大便成形；四君子汤组大鼠在皮毛、饮食、睡眠与大便状态改善方面明显；柴胡疏肝散组大鼠在行为状态、活跃程度、情绪反应等方面均见明显好转。
2.肝郁脾虚证模型大鼠体重的变化及相关方药的作用：实验期间,正常组大鼠体重明显增加,模型组与3个给药组大鼠体重增加较为缓慢,其中模型组、柴疏四君汤组和四君子汤组大鼠在第1周末体重出现负增长；模型组与柴胡疏肝散组大鼠在第4周末体重出现下降趋势。与正常组比较,模型组与柴疏四君汤组、四君子汤组、柴胡疏肝散组大鼠在第1w、2w、3w、4w末的体重均明显降低,差异具有显著性意义(P<0.05)。与模型组比较,3个给药组大鼠体重变化无显著性差异(P>0.05)；且3个给药组间大鼠体重变化无明显差异(P>0.05)。
3.肝郁脾虚证模型大鼠自主行为的变化及相关方药的作用：与正常组比较,造模第14天时的模型组与3个中药组大鼠的爬行格数明显增加,差异具有显著性意义(P<0.01或P<0.05)；模型组、柴疏四君汤组大鼠直立次数增加,差异具有显著性意义(P
4.肝郁脾虚证模型大鼠中枢神经生化指标的变化及相关方药的作用：(1)与正常组比较,模型组大鼠海马组织中Asp(天冬氨酸)的含量呈升高趋势,Glu(谷氨酸)、GABA(Y-氨基丁酸)、Gly(甘氨酸)、Tau(牛磺酸)的含量呈下降趋势,但差异均无显著性意义(P>0.05)；下丘脑组织中PGE2和cAMP的变化均无显著性差异(P>0.05)；脑干P450酶活性与酶含量的变化均无显著性差异(P>0.05)。(2)与模型组比较,3个中药组大鼠的上述指标均无明显变化(P>0.05)。
研究结论：采用慢性束缚+饮食失节+过度疲劳法制备的肝郁脾虚证模型大鼠表现出活动减少、扎堆多睡、情绪低落、争斗减少、饮食减少,皮毛枯乱,大便稀溏、体重减轻等,同时伴有自主活动增强的行为特征。经柴疏四君汤、四君子汤、柴胡疏肝散治疗2周后,可使模型大鼠外观表征呈现不同程度的改善,并对自主活动具有一定调节作用,其中以柴疏四君汤的干预效果最佳,柴胡疏肝散和四君子汤在改善模型大鼠外观表征中的行为状态、情绪反应和皮肤毛发、睡眠状态等方面各有侧重。结果表明,该模型具有类似于肝郁脾虚证的中医证候的一些特点,柴疏四君汤与该证模型具有更高的关联性,符合“疏肝健脾与肝郁脾虚证相应”的中医证治经验。
本研究为肝郁脾虚证模型的中医证候学评价提供一定的研究思路,为理解“方证相关”的内涵及认识相关方剂的功用提供了一定的现代依据。
Prescription is a tool with a specific function and the main treatment for disease prevention, Which is made by a number of herbs compatibility. There is a a high degree of correlation or focused references between the compatibility their primary disease pathogenesis or pathological evidence. This is called "The correlation between formula and syndrome."Evidence for a specific disease may have a few formulas work, but the results are different, or the same role in different disease and syndrome prescriptions would be different treatment. "The correlation between formula and syndrome" is the core principle of traditional Chinese medicine dialectical thinking, but also to learn prescription based on the logic of justification. Study the relationship between the formula and the syndrome to reveal the syndrome differentiation theory has important theoretical and practical significance.
this study in rats with chronic astricting+diet+excess fatigue to replicate animal model of liver depression and spleen deficiency.To act as entry points from the appearance of animal model to compare the observations of rats'the appearance of behavioral change on the role of the differences and similarities, with the Liver, Spleen, Liver Spleen different effects of chaihushugansan. Sijunzitang and chaishusijuntang.And then and the ascertain the central neurotransmitters and biochemical changes of the model animal and and the changes result in the different formulae.
This dissertation contains of literature review and experimental research. Research evolutions of clinic and experiment about the model of stagnation of liver and deficiency of spleen (GYPX), chaihushugansan. Sijunzitang and chaishusijuntang are summed up.Experimental study observed stagnation and spleen deficiency syndrome in rats characterized by the appearance of behavior and central neurotransmitters and related biochemical changes in things and chaihushugansan. Sijunzitang and chaishusijuntang. relevant role of the models.
Methods:Rats were randomly divided into normal control group, liver depression and spleen deficiency syndrome group (hereafter referred to as the model group), chaishusijuntang groups,SiJunzi tang group and chaihushugansan group. Each group has 12 annimals. the latter 4 groups of rats were placed in restraint devices every day 8:00 am restriction of 3 h,2:00 pm place filled with warm water (22±1℃) swimming in a large plastic bucket 10 min, every other day feeding (every other day ban food, enough to eat every other day) for 4 weeks; normal control group did not exert any stimulating natural feeding. At 15 days of modeling, the rats were treated with traditional Chinese medicine Chaishusijun Tang 4.27g/kg, Sijuzitang 4.53g/kg, ChauhuShugan San 4.2g/kg orally,1 time per day; model group with the control group were given distilled water for 14 days. And in the first 7d,14d,21d,28d, points early, middle and later time points the rats were observed and recorded changes in the behavior of state, activity level, emotional reactions, skin hair, food intake, sleep, stool state, etc.; In the first 7 days a week 2:00-2:30 pm Determination of body weight of rats in each group; in the first 14d,28d by open field test rats were recorded within 5min crawling cell number, number of rearing, modification time and Time on the central grid.8:00 am on the 29th day were decapitated, rapidly stripping the Ice hippocampus, hypothalamus and brain stem, placed in liquid nitrogen tanks stored, tested. High Performance Liquid Chromatography and Fluorescence Detection hippocampus Asp, Glu, GABA, Gly, Tau; measured by radioimmunoassay in the hypothalamus of cAMP, PGE2; by enzyme-linked immunosorbent assay in the brain stem P450 enzyme activity and content.
Statistical Methods:The data were to described an x±S, After the single factor analysis of variance (one-way ANOVA) to test, the more groups were analyzed using Student Newman Keuls Test test. All data using SPSS 13.0 for windows statistical processing software.
Results:1. Syndrome Model of rats and related changes in appearance characterized the role of herbs:1 week after modeling, model group, chaishusijuntang group, SiJunzitang group, chaihushugansan group's behavioral activity, emotional reactions, skin hair, diet, sleep and defecate state all did not change. Model rats 2 weeks after modeling showed reduced activity, reduced the level of activity, mood irritability, food intake, fur ring true Chak, easy to wake up, then dry, etc.; 3 weeks after modeling,the model group began to slow down the movement, emotions stability, food intake, fur is not Chak, tired of lying, loose stools; 4 weeks after modeling, the significant reduction of activities, get together or even tired of lying to sleep, emotional state from the beginning of the irritability to depression, the struggle to reduce, food intake, coat dry mess, loose stool and so on. Compared with model group, the rats in the administration of Chinese medicine after 1 week (3 weeks after modeling), activity, mood stabilization, food has increased, fur, sleep and bowel movements were seen in varying degrees of improvement in the state. After 2 weeks of administration (4 weeks of modeling), chaishusijuntang group significantly increased behavioral activity, responsive, smooth fur close to the whole, food increased, the depth of sleep, moderate, formed stool;sijuzitang grope, the rats'fur, food, sleep and improvement of stool condition obviously; rats of chaihushugansan in behavioral state, activity level, emotional response and so on were see significant improvement.
2. Syndrome Model of body weight change and related prescriptions in Action: During the experiment, body weight of the normal rats was significantly increased,while the body weight in model group and three treated group gained weight more slowly, in which the model group, chaishusijuntang Group and sijunzitang group body weight had a negative growth in the first weekend. The weigh of the model group rats, chauhushugansan group showed a downward trend,after 4 weeks.Compared with normal group, the body weight of model group and chaishusijuntang group, SiJunzitang group, chaihushugansan group were significantly decreased at the end of 1w,2w,3w,4w. the difference was significant (P <0.05). Compared with model group, three treated group no significant changes in body weight difference (P> 0.05); and three dose groups no significant difference in body weight change (P> 0.05).
3. Syndrome Model of autonomous behavior in rats and related changes in the role of herbs:Compared with normal group, he number of crawling cells of model group and the three Chinese medicine groups significantly increased (P<0.01 or P <0.05) in the first 14 days of modeling, the difference; The rats of model group and chaishusijuntang vertical had increased, the difference was significant (P<0.05); model group, sijunzitang group modification time and the central grid residence time were extended, of which modifiede time'difference was significant (P<0.05). After 2 weeks of administration (At the 28th day), compared with the normal group, the number of rats crawling cells increased model group, sijunzitang group and chaishusijuntang group, the differences were significant (P<0.05), the number of rats crawling cells of chaishusijuntang close to the normal level (P> 0.05); The model group and sijunzitang group vertical increased in the number, the difference was significant (P<0.05), chaishusijuzitang group and chaihushugans group didn't increased obviously (P> 0.05); The modification time and time of he central cell residence of model group and three Chinese medicine group, were extended, but the difference was not significant (P> 0.05). Compared with model group, crawling cell number and were s number of rearing of 3 Chinese medicine groups significantly lower. the number of crawling cells of chaishusijuntang group reduced significantly, the difference was significant (P<0.05).
4. Syndrome Model of central nervous and related biochemical changes in the role of prescriptions:(1) Compared with with the normal group, hippocampus Asp (aspartic acid) of model group content tended to increase Glu (glutamic acid), GABA (y-aminobutyric acid), Gly (glycine), Tau (taurine) were decreased, but the differences were not significant (P> 0.05); PGE2 and cAMP in the hypothalamus changed not significantly different (P> 0.05); brainstem P450 enzyme activity and enzyme content in no significant difference (P> 0.05). (2) Compared with model group, three Chinese medicine group had no significant change in the above index (P> 0.05).
Conclusions:The chronic restraint+diet+excess fatigue Disloyalty prepared Syndrome Model of rats showed reduced activities, get together to sleep, depression, fighting less, eating less, fur dry mess, loose stool, weight loss and so on, accompanied by the enhanced spontaneous activity behavior.2 weeks after the treat with chaishusijuntang, sijunzitang, chaihushugansan, rats can characterize the appearance of varying degrees of improvements and self-regulate certain activities.Then intervention effct of chaihusijuntang group is best,chauhushugansan group and sijuzitang has had play respective role in the behavioral state,emotional reactions and the skin hair, sleep and so on. These results show that the model is similar to the stagnation and spleen deficiency syndromes in some features, chaishusijuntang and this model has a higher correlation, consistent with "Shuganjianpi corresponding spleen deficiency and stagnation" in TCM experience.
This study Syndrome Model of Syndrome Evaluation study provides some ideas for evaluating TCM Syndrome.lt also can provided some of modern basis for understanding the meaning"evidence related parties" and function of the relevant formulas.
引文
1.吴圣贤,方素钦,王映辉,等.中医肝郁脾虚证症状分布和特征专家问卷调查研究[J].北京中医药大学学报,2007,30(12)：854-856.
2.郑开梅,武成,薛蕾,等.抑郁症中医证候学临床流行病学调查[J].天津中医药大学学报,2006,25(3)：170-171.
3.王文萍,李晓斌,王天芳,等.应用临床流行病学调查方法提取抑郁症的中医证候主、次症状[J].环球中医药,2009,2(2)：110-112.
4.陈泽奇,胡随瑜,张海男,等.抑郁症肝郁脾虚证证候标准专家问卷分析[J].中国现代医学杂志,2002,12(20)：10-12.
5.赵玉秋,陈国林,陈泽奇,等.肝郁脾虚证临床流行病学调查[J].中国现代医学杂志,1998,8(12)35-37.
6.肖桂林,金益强,鄢东红,等.肝郁脾虚证实验诊断指标的研究[J].湖南中医学院学报,1998,18(2)：4-5.
7.马玉平,王天芳,薛晓琳,等.肝郁脾虚证的症状特点及辨证标准的现代文献研究[J].中华中医药杂志,2006,21(2)：89-92.
8.陈泽奇,胡随瑜,张海男,等.抑郁症常见中医证候标准的研究[J].中医杂志,2005,46(1)：47-49.
9.宋炜熙,金益强,鄢东红,等.肝系不同证候血浆去甲肾上腺素和肾上腺素含 量分析[J].山东中医药大学学报,2004,28(2)：110-113.
10.金益强,胡随瑜,张翔,等.中医肝不同证候血浆去甲肾上腺素和肾上腺素含量及植物神经功能的研究[J].中国中西医结合杂志,1998,18(11)：655-657.
11.李晓照,陈泽奇,胡随瑜,等.抑郁症患者血清脑源性神经营养因子水平与辨证分型关系分析[J].湖南中医学院学报,2005,25(4)：30-34.
12.黎杰群.肝郁脾虚证患者血浆环核苷酸的变化[J].湖南医学院学报,1985,10(4)：351.
13.杨英,关茂会,李艳荣,等.慢性肝炎患者血清T3、T4变化与中医辨证分型的联系[J].中西医结合杂志,1986,6(6)：341.
14.谭行华,肖真,杨克彬,等.慢性肝炎中医分型与内分泌激素的关系[J].中国中西医结合杂志,1995,15(10)：604-605.
15.刘文兰,李秀惠,张炎,等.慢性乙型肝炎主要证型血清生长激素水平的实验研究[J].北京中医药大学学报,2007,14(5)：11-12.
16.陈锦芳,张桂英.慢性乙型肝炎肝郁脾虚证TNF-α、IL-6水平研究[J].福建中医学院学报,2009,19(4)：15-16.
17.楼孝惠,陈智,黄茵,等.慢性乙型肝炎中医证型与IL-2、IL-10、IL-12、IFN-γ水平的关系初探[J].中西医结合肝病杂志,2001,11(5)：282.
18.刘学俭.乙肝病毒感染中医证型与免疫功能的相关性研究[J].贵阳中医学院学报,2008,30(1)：6-7.
19.周虎,周萍,俞庆福.慢性病毒性肝炎T淋巴细胞亚群、免疫球蛋白变化与中医证候关系探讨[J].江西中医学院学报,2001,13(2)：49.
20.彭汉光,邱明义,张茂林,等.加味四逆散对肝郁脾虚者可溶性细胞粘附分子-1水平和单核细胞功能的影响[J].华中科技大学学报,2003,32(6)：634-636.
21.肖桂林,金益强,鄢东红,等.单纯脾气虚证与肝郁脾虚证内在差别的实验研究[J].江西中医学院学报,2000,12(1)：34-35.
22.张俊富,崔丽安.慢性肝炎及肝硬化辨证分型与血清肝纤维化指标的关系[J].中西医结合肝病杂志,1995,5(4)：10-11.
23.任平,黄熙,李双庆,等.脾气虚、肝郁脾虚及胃实热证患者阿魏酸药代动力学特征比较[J].中西医结合学报,2006,4(2)：147-151.
24.陈国桢.肝郁脾虚证的本质探讨[J].中西医结合杂志,1985,5(12)：732-735.
25.邝元亮,颜文明.肝郁脾虚证血液流变性之初步研究[J].湖南中医学院学报,1989,9(2)：101.
26.田广俊,芮玩珠,陈培琼,等.柴芍六君子汤联合恩替卡韦治疗慢性乙型肝炎(肝郁脾虚证)30例临床观察[J].广州中医药大学学报,2009,26(3)：218-220.
27.李莉,郑舜华,李刚,等.柴芍六君子汤加减治疗肝郁脾虚型慢性萎缩性胃炎临床观察[J].上海中医药杂志,2009,43(3)：26-28.
28.熊之焰,李帅军,桂平.四君子汤合痛泻要方加减治疗肝郁脾虚型溃疡性结 肠炎49例临床观察[J].中医药导报,2006,12(2)：39-41.
29.程立新,曹志群,柳春兰,等.香芪利胆煎治疗慢性胆囊炎肝郁脾虚证临床观察[J].山东中医药大学学报,2004,28(3)：201-202.
30.徐超极,刘红茹,刘红英.中医针药联合治疗肠易激综合征肝郁脾虚证的分析研究[J].云南中医中药杂志,2008,29(12)：17-18.
31.陈国桢,金益强,李学文,等.肝郁脾虚的理论与实验研究[J].湖南医学院学报,1979,4(3)：131.
32.郑旭锐,张航,李小苗,等.肝郁脾虚证肝纤维化大鼠模型研究[J].陕西中医学院学报,2008,31(6)：54-57.
33.徐珊,包剑锋,周敏,等.肝纤维化病证结合模型的研制[J].中国中医药科技,2009,16(2)：81-83.
34.郭振球,赵晓威.肝纤宁对肝郁脾虚大鼠的保肝抗纤作用[J].湖南中医学院学报,1998,18(2)：10.
35.韩秋艳.肝郁脾虚证动物模型的建立[J].贵阳中医学院报,2001,23(3)：59.
36.顾立刚,郭学志,王庆国.大鼠溃疡性结肠炎肝郁脾虚证模型的研究[J].北京中医药大学学报,1999,22(2)：21.
37.顾立刚,郭学志,王庆国,等.疏肝健脾方对溃疡性结肠炎肝郁脾虚证大鼠结肠溃疡的影响[J].北京中医药大学学报,2000,23(4)：24.
38.张芳艳,毛新民,武鸿莉,等.肝郁脾虚型溃疡性结肠炎大鼠的免疫学研究[J].新疆医科大学学报,2004,27(4)：367.
39.岳利峰,丁杰,陈家旭,等.肝郁脾虚证大鼠模型的建立与评价[J].北京中医药大学学报,2008,31(6)：396-400.
40.李艳彦,谢鸣,陈禹,等.一种运用复合病因造模法复制大鼠肝郁脾虚证模型的研究[J].中国中医基础理论医学杂志,2006,12(6)：439-442.
41.顾立刚,郭学志,王庆国.大鼠溃疡性结肠炎肝郁脾虚证模型的研究[J].北京中医药大学学报,1999,22(2)：21-23.
42.梁媛,陈家旭,郭晓玲,等.逍遥散对肝郁脾虚证大鼠边缘系统神经元超微结构的影响[J].中华中医药杂志,2009,24(5)：577-581.
43.丁杰,陈家旭,饶红梅,等.逍遥散对肝郁脾虚证模型大鼠中枢GluRl、GluR2表达的影响[J].北京中医药大学学报,2009,32(6)：389-393.
44.李艳彦,谢鸣,陈禹,等.肝郁脾虚证模型大鼠下丘脑-垂体-肾上腺皮质的变化[J].现代生物医学进展,2006,6(4)：10-15.
45.丁杰,陈家旭,梁媛,等.逍遥散对肝郁脾虚证模型大鼠外周促肾上腺皮质激素、皮质酮的调节作用[J].中华中医药杂志,2009,24(11)：1436-1439.
46.李艳彦,谢鸣,王洪海,等.肝郁脾虚证模型大鼠甲状腺轴的变化及柴疏四君汤的作用观察[J].中国中医基础医学杂志,2008,14(3)：191-192.
47.王玉杰，谢鸣,阎玥,等.疏肝方、健脾方、疏肝健脾方对肝郁脾虚证模型 大鼠IL-2、IL-6及T淋巴细胞增殖率的影响[J].北京中医药大学学报,2009,32(6)：398-401.
48.李艳彦,谢鸣,陈禹,等.肝郁脾虚证大鼠模型复制中的免疫系统变化[J].中华中医药杂志,2006,21(7)：428-429.
49.彭桂英,顾立刚,王庆国,等.疏肝健脾方药对肝郁脾虚证荷瘤小鼠腹腔巨噬细胞功能的影响[J].中国中医药信息杂志,2003,10(2)：29-31.
50.张芳艳,毛新民,武鸿莉,等.肝郁脾虚型溃疡性结肠炎大鼠的免疫学研究[J].新疆医科大学学报,2004,27(4)：367-369.
51.刘金铃,姚良权,聂陆安.疏肝健脾治疗与肝郁脾虚因素刺激对大肠癌大鼠免疫功能变化的探讨[J].国际医药卫生导报,2006,12(3)：4-6.
52.陈德兴,王雨秾,沈芸,等.半夏泻心汤对肝郁脾虚大鼠生长抑素和胃动素的影响[J].上海中医药杂志,2006,40(6)：56-58.
53.顾力刚,王济,张前,等.肝郁脾虚因素刺激对大鼠实验性肝癌发生和鸟氨酸脱羧酶表达的影响[J].中国中医药信息杂志,2005,12(1)：35-37.
54.唐亚平,龚超奇,黄秋粤,等.肝郁脾虚证大鼠TXB2、6-Keto-PGF含量的观察研究[J].世界中医药,2009,4(5)：287-288.
55.李艳彦,谢鸣,王洪海,等.肝郁脾虚证模型大鼠血流变及TXB2、PGF 1 a的变化[J].现代生物医学进展,2007,7(1)：15-18.
56.徐珊,包剑锋,周敏,等.肝纤维化不同证型与TGF-β1／Smad基因蛋白表达关系的实验研究[J].中华中医药学刊,2010,28(1)：23-28.
57.罗和古,丁杰,岳广欣,等.大鼠肝郁脾虚证的代谢组学研究[J].中西医结合学报,2007,5(3)：307-313.
1.关晓光,安春平,雪平,等.柴胡疏肝散加减治疗抑郁症30例临床观察[J].中国中医药杂志,2007,14(5)：330.
2. 王光林,靳燕宾.柴胡疏肝散加味联合盐酸帕罗西汀治疗中重度卒中后抑郁临床观察[J].中西医结合心脑血管病杂志,2009,7(12)：1428-1429.
3.刘俊红.柴胡疏肝散合针刺治疗中风后抑郁症疗效观察[J].实用诊断与治疗杂志,2006,20(10)：776-777.
4.蔡秀巧.柴胡疏肝散加减治疗带状疱疹后遗神经痛32例[J].山东中医杂志,2007,26(9)：618-619.
5.康田.柴胡疏散加味治疗带状疱疹50例[J].云南中医中药杂志,2007,28(9)：22.
6. 陈金红.柴胡疏肝散治疗胃神经官能症81例[J].实用中医药杂志,2006,22(12)：746-747.
7. 张英学,谭毅.柴胡疏肝散加味治疗不寐43例[J].新中医,2004,36(3)：59.
8.张敏,虹娜,熊云,等.柴胡疏肝散配合针刺治疗紧张型头痛40例[J]. Chinese Journal of Information on TCM,2006,13(9):60.
9. 芮以融.柴胡疏肝散加减治疗胆胃食管反流病60例[J].中国中西医结合消化杂志,2009,17(3)：200-201.
10.朱雪琼,朱雪梅,朱建龙,等.柴胡疏肝散加减治疗慢性胃炎60例[J].山东中医杂志,2009,28(3)：177.
11.宋庆红,王定康.柴胡疏肝散加味治疗肠易激综合征69例[J].实用中医药杂志,2009,25(4)：225.
12.杜生华.柴胡疏肝散治疗慢性胰腺炎120例报告[J].甘肃中医,2003,16(9)：15.
13.张红.疏肝健脾法治疗功能性消化不良50例[J].时珍国医国药,2009,20(6)：1537-1538.
14.潘丰满,黄江荣.柴胡疏肝散治疗非酒精性脂肪肝82例临床观察[J].时珍国医国药,2009,20(8)：2010-2011.
15.李跃.加味柴胡疏肝散治疗冠心病心绞痛41例临床观察[J].北京中医,2006,25(1)27-29.
16.张新元.柴胡疏肝散加味治疗胸痹心痛的临床研究[J].社区中医药,2009,25(1)：35.
17.邵淑霞,康莲香.柴胡疏肝散加味治疗经前期紧张综合征60例[J].吉林中医药,2007,27(7)：33.
18.邓火生,钭妙莺.柴胡疏肝散加味治疗乳腺病88例临床观察[J].中国医药指南,2009,7(20)：105-106.
19.严宇仙.柴胡疏肝散加味治疗不孕症[J].浙江中西医结合杂志,2003,13(8)：509-510.
20.张兴正.柴胡疏肝散加减治疗瘿瘤120例[J].四川中医,2006,24(8)：55-56.
21.沈美玉,林丽珠,李永浩.疏肝理气在乳腺肿瘤治疗中的应用[J].时珍国医国药,2001,12(5)：434.
22.严亨秀,任昉,顾健.柴胡疏肝散对实验性肝郁证大鼠的影响[J].中药药理与临床2006,22(6)：5-6.
23.朱清静,罗欣拉,熊振芳.柴胡疏肝散对慢性束缚应激性肝郁证大鼠下丘脑-垂体-肾上腺轴的调节作用[J].湖北中医杂志,2003,25(11)：7-8.
24.陈松,李家邦,朱双罗,等.肝郁证T、B淋巴细胞活性改变及疏肝治疗影响的实验研究[J].湖南中医学院学报,2001,21(2)：7-8.
25.杨冬花,李家邦,郑爱华,等.肝气郁结证模型大鼠Thl／Th2细胞因子变化及柴胡疏肝散的干预作用[J].湖南中医学院学报,2003,23(5)：4-7.
26.陈梁,朱锦善,任建平.柴胡疏肝散对四氯化碳所致大鼠急性肝损伤的防治作用[J].中西医结合肝病杂志,2004,14(1)：42-43.
27.冯育航,董湘玉.柴胡疏肝散对应激状态下大鼠胃溃疡的治疗[J].中国现代药物应用,2007,1(10)：26-27.
28.敖海清,徐志伟,严灿.柴胡疏肝散及逍遥散对慢性心理应激大鼠血清皮质酮及胃肠激素的影响[J].中药新药与临床药理,2007,18(4)：288-291.
29.凌江红,韦连明,张钰琴.疏肝理气法对功能性消化不良大鼠下丘脑胃血浆胃泌素的影响[J].辽宁中医杂志,2009,36(10)：1812-1813.
30.吴先哲.柴胡疏肝散对心理应激大鼠行为学的影响[J].中国实验方剂学杂志,2006,12(3)：38-40.
31.凌江红,张钰琴,梁纲.疏肝理气法对夹尾应激大鼠行为学及胃组织学的影响[J].世界华人消化杂志,2009,17(3)：299-302.
32.孙占杰.加味四君子汤治疗动力障碍型功能性消化不良60例[J].山西中医,2009,25(1)：16.
33.金贤兰.四君子汤加减治疗功能性消化不良60例[J].长春中医药大学学报,2007,23(6)：33.
34.高晔.四君芍药汤治疗溃疡性结肠炎50例[J].河北中医药学报,2008,23(1)：30.
35.蔡晓静,付玉军,朱本元.加味四君子汤保留灌肠治疗溃疡性结肠炎30例[J].新中医,2009,41(60)：85-86.
36.石爱华.电热针结合四君子汤加味治疗脾胃虚寒型慢性萎缩性胃炎临床观察[J].河北中医,2009,31(3)：418-420.
37.李景花.四君子汤合丹参饮加减治疗慢性萎缩性胃炎46例[J].四川中医,2009,27(8)：89.
38.杨洁.四君子汤配合四逆散治疗肠易激综合征临床研究[J].湖北中医杂志,2009,31(7)：16-17.
39.马纯清.四君子汤合四神丸加减治疗慢性泄泻临床观察[J].光明中医,2009,24(11)：2119-2120.
40.温庆祥,古颖.四君子汤对脾虚患者免疫功能影响[J].北京中医,2006,25(4)：239-240.
41.章梅,张仲海,夏天.四君子汤对脾虚患者血清可溶性细胞粘附分子-1水平和单核细胞功能的影响[J].中国中西医结合杂志,1999,19(5)：270-272.
42.华玉淑,唐汉庆.四君子汤加减治疗老年慢性支气管炎54例[J].长春中医药大学学报,2009,25(4)：517-518.
43.郑伟鸿,郑伟达,郑东海.扶正固本法治疗恶性肿瘤经验[J].世界中西医结合杂志,2009,4(4)：292.
44.周峰,李传刚,刘用楫.四君子汤在膀胱癌治疗中的应用及研究进展[J].大连医科大学学报,2008,30(5)：473-475.
45.王海燕,朱跃科,陈煜.四君子汤防治大鼠应激性胃溃疡的初步研究[J].世界华人消化杂志,2005,13(13)：1595-1596.
46.郑小伟,宋红,包素珍,等.实验性脾气虚大鼠胃泌素的基因表达及四君子汤的干预作用[J].中华中医药杂志,2008,23(3)：264-266.
47.任平,黄熙,谢良杰.四君子汤对脾虚模型大鼠胃动素和前列腺素E2含量的影响[J].中药药理与临床,1994,6：7-8.
48.任平,黄熙,张莉.四君子汤对实验性脾虚大鼠胃排空率的影响[J].中国中西医结合杂志,2000,20(8)：596-598.
49.易崇勤,孙建宁,张家俊,等.四君子汤调整小鼠运化功能紊乱的实验研究[J].中国中西医结合杂志,1997,17(1)：42-44.
50.王洪海.四君子汤、柴疏四君汤、柴胡疏肝散作用于脾虚证大鼠模型的生物效应比较[D].北京：北京中医药大学,2007,6.
51.陈文强,黄小波,李宗信,等.四君子汤对脾虚大鼠不同脑区单胺类神经递质含量的影响[J].天津中医药,2009,26(2)：137-138.
52.李志强,陈津岩,何赞厚,等.四君子汤对脾虚证大鼠血清性激素和甲状腺激素水平的影响[J].河南中医,2008,28(3)：36-37.
53.李志强,陈津岩,何赞厚,等.四君子汤对脾虚证大鼠性激素和环核苷酸水平的影响[J].实用中医药杂志,2008,24(10)：619-620.
54.李家邦,陈松,李立新,等.四君子汤对脾虚证模型大鼠淋巴细胞功能的影响[J].成都中医药大学学报,2001,24(3)：31-32.
55.邢燕玲,游俊.四君子汤对脾气虚型慢性萎缩性胃炎大鼠外周血T淋巴细胞亚群的影响[J].湖北中医学院学报,2007,9(2)：18-19.
56.杨冬花,李家邦,郑爱华,等.脾气虚证模型大鼠Thl／Th2细胞因子的失衡以及四君子汤的干预作用[J].中国医师杂志,2004,6(2)：181-182.
57.章梅,夏天,张仲海.脾虚小鼠红细胞免疫和腹腔巨噬细胞吞噬功能改变的实验研究[J].北京中医药大学学报,1999,22(3)：26-27.
58.梁尚华,路长林,邹军,等.四君子汤对慢性应激大鼠行为学及免疫指标作 用的研究[J].成都中医药大学学报,2005,28(2)：38-40.
59.王洪海.四君子汤、柴疏四君汤、柴胡疏肝散作用于脾虚证大鼠模型的生物效应比较[D].北京：北京中医药大学,2007,6.
60.梁尚华,路长林,邹军,等.四君子汤对慢性应激大鼠行为学及免疫指标作用的研究[J].成都中医药大学学报,2005,28(2)：38-40.
61.王奇,陈云波,冯炯,等.不同治法方药对快速老化小鼠学习记忆功能的影响[J].中药药理与临床,2009,25(5)：5-7.
62.成文利,江振友,王修银,等.四君子汤及拆方对D-半乳糖诱导衰老小鼠学习记忆调节作用的影响[J].中药材,2008,31(7)：1039-1041.
63.王世荣.疏肝健脾和胃法治疗功能性消化不良疗效观察[J].吉林中医药,2008,28(6)：411-412.
64.练慧,张正利.柴胡疏肝散合四君子汤加减治疗慢性萎缩性胃炎47例[J].上海中医药杂志,2006,40(5)：27-28.
65.罗改云,马羽萍,赵玲.柴胡疏肝散合六君子汤治疗慢性乙型病毒性肝炎60例[J].陕西中医,2007,28(2)：165-167.
66.施正康.疏肝健脾法治疗胃脘痛的临床观察[J].辽宁中医杂志,2004,31(10)：831.
67.李艳彦,谢鸣,王洪海,等.肝郁脾虚证模型大鼠甲状腺轴的变化及柴疏四君汤的作用观察[J].中国中医基础医学杂志,2008,14(3)：191-195.
68.王桐生,阎玥,王玉杰,等.柴疏四君汤对肝郁脾虚大鼠下丘脑-垂体-肾上腺皮质轴变化的调整作用[J].安徽中医学院学报,2009,28(3)：29-31.
69.王玉杰,谢鸣,阎玥,等.疏肝方、健脾方、疏肝健脾方对肝郁脾虚证模型大鼠IL-2、IL-6及T淋巴细胞增殖率的影响[J].北京中医药大学学报,2009,32(6)：398-401.
1.谢鸣.“方证相关”逻辑命题及其意义[J].北京中医药大学学报,2003,26(2)：11-12.
2.肖桂林,金益强,鄢东红,等.肝郁脾虚证实验诊断指标的研究[J].湖南中医学院学报,1998,18(2)：4.
3.郑爱华,李家邦,蔡光先,等.肝气郁结证与脾气虚证的Th细胞分化中的相关性实验研究[J].中国医师杂志,2004,6(3)：357.
4.严灿,等.加减四逆散对慢性心里应激大鼠胸腺糖皮质激素受体作用的研究[J].中国中西医结合杂志,2002,22(9)：196.
5.刘建平.柴胡疏肝散合并氟西汀治疗抑郁症的临床观察[J].山西中医学院学报,2001,2(4)：31-33.
6.黄仕文.柴胡疏肝散临床应用现状[J].山西中医,2001,17(2)：74.
7.李家邦,杨冬花,蒋荣鑫,等.N F-ATc在肝气郁结、脾气虚证模型大鼠的表达以及柴胡疏肝散、四君子汤的干预作用[J].中国现代医学杂志,2005,15(10)：1515-1517.
8.李艳彦.肝郁脾虚证的模型复制及相关方剂作用的生物学基础[D].北京：北京中医药大学,2006.
9.阎玥,谢鸣,王玉杰,等.疏肝、健脾、疏肝健脾方对肝郁脾虚证模型大鼠外观表征的影响.中国科技论文在线,200906-1175.
1. 陈奇.中药药理研究方法学[M].北京：人民卫生出版社,1994,669.
2.吴圣贤,方素钦,王映辉,等.中医肝郁脾虚证症状分布和特征专家问卷调查研究[J].北京中医药大学学报,2007,30(12)：854-856.
3.曹贵东,崔志明.“解郁健脾汤”治疗34例肝郁脾虚证的临床观察[J].中医药研究,1999,15(4)：25-26.
4. 韩秋艳.肝郁脾虚证动物模型的建立[J].贵阳中医学院报,2001,23(3)：59.
5.徐叔云,卞如廉,陈修.药理实验方法学[M].2版.北京：人民卫生出版社,1991：642-643.
6.刘克嘉，邬勤娥.应激与应激性疾病[M].北京：人民军医出版社,1991：297-300.
7.岳利峰,丁杰,陈家旭,等.肝郁脾虚证大鼠模型的建立与评价[J].北京中医药大学学报,2008,31(6)：396-400.
8. 阎玥,谢鸣,王玉杰,等.疏肝、健脾、疏肝健脾方对肝郁脾虚证模型大鼠外观表征的影响.中国科技论文在线,200906-1175.
9.王阶,张兰凤,王永炎.方证对应理论源流及临床研究[J].世界科学技术.中医药现代化-基础研究,2006,6(4)：13-16.
10.张丽萍,张曼,陈友友,等.加味温胆汤对抑郁模型大鼠学习记忆能力及海马cAMP-PKA途径的影响[J].中国康复医学杂志,2008,23(12)：1082-1084.
2.郑开梅,武成,薛蕾,等.抑郁症中医证候学临床流行病学调查[J].天津中医药大学学报,2006,25(3)：170-171.
3.王文萍,李晓斌,王天芳,等.应用临床流行病学调查方法提取抑郁症的中医证候主、次症状[J].环球中医药,2009,2(2)：110-112.
4.陈泽奇,胡随瑜,张海男,等.抑郁症肝郁脾虚证证候标准专家问卷分析[J].中国现代医学杂志,2002,12(20)：10-12.
5.赵玉秋,陈国林,陈泽奇,等.肝郁脾虚证临床流行病学调查[J].中国现代医学杂志,1998,8(12)35-37.
6.肖桂林,金益强,鄢东红,等.肝郁脾虚证实验诊断指标的研究[J].湖南中医学院学报,1998,18(2)：4-5.
7.马玉平,王天芳,薛晓琳,等.肝郁脾虚证的症状特点及辨证标准的现代文献研究[J].中华中医药杂志,2006,21(2)：89-92.
8.陈泽奇,胡随瑜,张海男,等.抑郁症常见中医证候标准的研究[J].中医杂志,2005,46(1)：47-49.
9.宋炜熙,金益强,鄢东红,等.肝系不同证候血浆去甲肾上腺素和肾上腺素含 量分析[J].山东中医药大学学报,2004,28(2)：110-113.
10.金益强,胡随瑜,张翔,等.中医肝不同证候血浆去甲肾上腺素和肾上腺素含量及植物神经功能的研究[J].中国中西医结合杂志,1998,18(11)：655-657.
11.李晓照,陈泽奇,胡随瑜,等.抑郁症患者血清脑源性神经营养因子水平与辨证分型关系分析[J].湖南中医学院学报,2005,25(4)：30-34.
12.黎杰群.肝郁脾虚证患者血浆环核苷酸的变化[J].湖南医学院学报,1985,10(4)：351.
13.杨英,关茂会,李艳荣,等.慢性肝炎患者血清T3、T4变化与中医辨证分型的联系[J].中西医结合杂志,1986,6(6)：341.
14.谭行华,肖真,杨克彬,等.慢性肝炎中医分型与内分泌激素的关系[J].中国中西医结合杂志,1995,15(10)：604-605.
15.刘文兰,李秀惠,张炎,等.慢性乙型肝炎主要证型血清生长激素水平的实验研究[J].北京中医药大学学报,2007,14(5)：11-12.
16.陈锦芳,张桂英.慢性乙型肝炎肝郁脾虚证TNF-α、IL-6水平研究[J].福建中医学院学报,2009,19(4)：15-16.
17.楼孝惠,陈智,黄茵,等.慢性乙型肝炎中医证型与IL-2、IL-10、IL-12、IFN-γ水平的关系初探[J].中西医结合肝病杂志,2001,11(5)：282.
18.刘学俭.乙肝病毒感染中医证型与免疫功能的相关性研究[J].贵阳中医学院学报,2008,30(1)：6-7.
19.周虎,周萍,俞庆福.慢性病毒性肝炎T淋巴细胞亚群、免疫球蛋白变化与中医证候关系探讨[J].江西中医学院学报,2001,13(2)：49.
20.彭汉光,邱明义,张茂林,等.加味四逆散对肝郁脾虚者可溶性细胞粘附分子-1水平和单核细胞功能的影响[J].华中科技大学学报,2003,32(6)：634-636.
21.肖桂林,金益强,鄢东红,等.单纯脾气虚证与肝郁脾虚证内在差别的实验研究[J].江西中医学院学报,2000,12(1)：34-35.
22.张俊富,崔丽安.慢性肝炎及肝硬化辨证分型与血清肝纤维化指标的关系[J].中西医结合肝病杂志,1995,5(4)：10-11.
23.任平,黄熙,李双庆,等.脾气虚、肝郁脾虚及胃实热证患者阿魏酸药代动力学特征比较[J].中西医结合学报,2006,4(2)：147-151.
24.陈国桢.肝郁脾虚证的本质探讨[J].中西医结合杂志,1985,5(12)：732-735.
25.邝元亮,颜文明.肝郁脾虚证血液流变性之初步研究[J].湖南中医学院学报,1989,9(2)：101.
26.田广俊,芮玩珠,陈培琼,等.柴芍六君子汤联合恩替卡韦治疗慢性乙型肝炎(肝郁脾虚证)30例临床观察[J].广州中医药大学学报,2009,26(3)：218-220.
27.李莉,郑舜华,李刚,等.柴芍六君子汤加减治疗肝郁脾虚型慢性萎缩性胃炎临床观察[J].上海中医药杂志,2009,43(3)：26-28.
28.熊之焰,李帅军,桂平.四君子汤合痛泻要方加减治疗肝郁脾虚型溃疡性结 肠炎49例临床观察[J].中医药导报,2006,12(2)：39-41.
29.程立新,曹志群,柳春兰,等.香芪利胆煎治疗慢性胆囊炎肝郁脾虚证临床观察[J].山东中医药大学学报,2004,28(3)：201-202.
30.徐超极,刘红茹,刘红英.中医针药联合治疗肠易激综合征肝郁脾虚证的分析研究[J].云南中医中药杂志,2008,29(12)：17-18.
31.陈国桢,金益强,李学文,等.肝郁脾虚的理论与实验研究[J].湖南医学院学报,1979,4(3)：131.
32.郑旭锐,张航,李小苗,等.肝郁脾虚证肝纤维化大鼠模型研究[J].陕西中医学院学报,2008,31(6)：54-57.
33.徐珊,包剑锋,周敏,等.肝纤维化病证结合模型的研制[J].中国中医药科技,2009,16(2)：81-83.
34.郭振球,赵晓威.肝纤宁对肝郁脾虚大鼠的保肝抗纤作用[J].湖南中医学院学报,1998,18(2)：10.
35.韩秋艳.肝郁脾虚证动物模型的建立[J].贵阳中医学院报,2001,23(3)：59.
36.顾立刚,郭学志,王庆国.大鼠溃疡性结肠炎肝郁脾虚证模型的研究[J].北京中医药大学学报,1999,22(2)：21.
37.顾立刚,郭学志,王庆国,等.疏肝健脾方对溃疡性结肠炎肝郁脾虚证大鼠结肠溃疡的影响[J].北京中医药大学学报,2000,23(4)：24.
38.张芳艳,毛新民,武鸿莉,等.肝郁脾虚型溃疡性结肠炎大鼠的免疫学研究[J].新疆医科大学学报,2004,27(4)：367.
39.岳利峰,丁杰,陈家旭,等.肝郁脾虚证大鼠模型的建立与评价[J].北京中医药大学学报,2008,31(6)：396-400.
40.李艳彦,谢鸣,陈禹,等.一种运用复合病因造模法复制大鼠肝郁脾虚证模型的研究[J].中国中医基础理论医学杂志,2006,12(6)：439-442.
41.顾立刚,郭学志,王庆国.大鼠溃疡性结肠炎肝郁脾虚证模型的研究[J].北京中医药大学学报,1999,22(2)：21-23.
42.梁媛,陈家旭,郭晓玲,等.逍遥散对肝郁脾虚证大鼠边缘系统神经元超微结构的影响[J].中华中医药杂志,2009,24(5)：577-581.
43.丁杰,陈家旭,饶红梅,等.逍遥散对肝郁脾虚证模型大鼠中枢GluRl、GluR2表达的影响[J].北京中医药大学学报,2009,32(6)：389-393.
44.李艳彦,谢鸣,陈禹,等.肝郁脾虚证模型大鼠下丘脑-垂体-肾上腺皮质的变化[J].现代生物医学进展,2006,6(4)：10-15.
45.丁杰,陈家旭,梁媛,等.逍遥散对肝郁脾虚证模型大鼠外周促肾上腺皮质激素、皮质酮的调节作用[J].中华中医药杂志,2009,24(11)：1436-1439.
46.李艳彦,谢鸣,王洪海,等.肝郁脾虚证模型大鼠甲状腺轴的变化及柴疏四君汤的作用观察[J].中国中医基础医学杂志,2008,14(3)：191-192.
47.王玉杰，谢鸣,阎玥,等.疏肝方、健脾方、疏肝健脾方对肝郁脾虚证模型 大鼠IL-2、IL-6及T淋巴细胞增殖率的影响[J].北京中医药大学学报,2009,32(6)：398-401.
48.李艳彦,谢鸣,陈禹,等.肝郁脾虚证大鼠模型复制中的免疫系统变化[J].中华中医药杂志,2006,21(7)：428-429.
49.彭桂英,顾立刚,王庆国,等.疏肝健脾方药对肝郁脾虚证荷瘤小鼠腹腔巨噬细胞功能的影响[J].中国中医药信息杂志,2003,10(2)：29-31.
50.张芳艳,毛新民,武鸿莉,等.肝郁脾虚型溃疡性结肠炎大鼠的免疫学研究[J].新疆医科大学学报,2004,27(4)：367-369.
51.刘金铃,姚良权,聂陆安.疏肝健脾治疗与肝郁脾虚因素刺激对大肠癌大鼠免疫功能变化的探讨[J].国际医药卫生导报,2006,12(3)：4-6.
52.陈德兴,王雨秾,沈芸,等.半夏泻心汤对肝郁脾虚大鼠生长抑素和胃动素的影响[J].上海中医药杂志,2006,40(6)：56-58.
53.顾力刚,王济,张前,等.肝郁脾虚因素刺激对大鼠实验性肝癌发生和鸟氨酸脱羧酶表达的影响[J].中国中医药信息杂志,2005,12(1)：35-37.
54.唐亚平,龚超奇,黄秋粤,等.肝郁脾虚证大鼠TXB2、6-Keto-PGF含量的观察研究[J].世界中医药,2009,4(5)：287-288.
55.李艳彦,谢鸣,王洪海,等.肝郁脾虚证模型大鼠血流变及TXB2、PGF 1 a的变化[J].现代生物医学进展,2007,7(1)：15-18.
56.徐珊,包剑锋,周敏,等.肝纤维化不同证型与TGF-β1／Smad基因蛋白表达关系的实验研究[J].中华中医药学刊,2010,28(1)：23-28.
57.罗和古,丁杰,岳广欣,等.大鼠肝郁脾虚证的代谢组学研究[J].中西医结合学报,2007,5(3)：307-313.
1.关晓光,安春平,雪平,等.柴胡疏肝散加减治疗抑郁症30例临床观察[J].中国中医药杂志,2007,14(5)：330.
2. 王光林,靳燕宾.柴胡疏肝散加味联合盐酸帕罗西汀治疗中重度卒中后抑郁临床观察[J].中西医结合心脑血管病杂志,2009,7(12)：1428-1429.
3.刘俊红.柴胡疏肝散合针刺治疗中风后抑郁症疗效观察[J].实用诊断与治疗杂志,2006,20(10)：776-777.
4.蔡秀巧.柴胡疏肝散加减治疗带状疱疹后遗神经痛32例[J].山东中医杂志,2007,26(9)：618-619.
5.康田.柴胡疏散加味治疗带状疱疹50例[J].云南中医中药杂志,2007,28(9)：22.
6. 陈金红.柴胡疏肝散治疗胃神经官能症81例[J].实用中医药杂志,2006,22(12)：746-747.
7. 张英学,谭毅.柴胡疏肝散加味治疗不寐43例[J].新中医,2004,36(3)：59.
8.张敏,虹娜,熊云,等.柴胡疏肝散配合针刺治疗紧张型头痛40例[J]. Chinese Journal of Information on TCM,2006,13(9):60.
9. 芮以融.柴胡疏肝散加减治疗胆胃食管反流病60例[J].中国中西医结合消化杂志,2009,17(3)：200-201.
10.朱雪琼,朱雪梅,朱建龙,等.柴胡疏肝散加减治疗慢性胃炎60例[J].山东中医杂志,2009,28(3)：177.
11.宋庆红,王定康.柴胡疏肝散加味治疗肠易激综合征69例[J].实用中医药杂志,2009,25(4)：225.
12.杜生华.柴胡疏肝散治疗慢性胰腺炎120例报告[J].甘肃中医,2003,16(9)：15.
13.张红.疏肝健脾法治疗功能性消化不良50例[J].时珍国医国药,2009,20(6)：1537-1538.
14.潘丰满,黄江荣.柴胡疏肝散治疗非酒精性脂肪肝82例临床观察[J].时珍国医国药,2009,20(8)：2010-2011.
15.李跃.加味柴胡疏肝散治疗冠心病心绞痛41例临床观察[J].北京中医,2006,25(1)27-29.
16.张新元.柴胡疏肝散加味治疗胸痹心痛的临床研究[J].社区中医药,2009,25(1)：35.
17.邵淑霞,康莲香.柴胡疏肝散加味治疗经前期紧张综合征60例[J].吉林中医药,2007,27(7)：33.
18.邓火生,钭妙莺.柴胡疏肝散加味治疗乳腺病88例临床观察[J].中国医药指南,2009,7(20)：105-106.
19.严宇仙.柴胡疏肝散加味治疗不孕症[J].浙江中西医结合杂志,2003,13(8)：509-510.
20.张兴正.柴胡疏肝散加减治疗瘿瘤120例[J].四川中医,2006,24(8)：55-56.
21.沈美玉,林丽珠,李永浩.疏肝理气在乳腺肿瘤治疗中的应用[J].时珍国医国药,2001,12(5)：434.
22.严亨秀,任昉,顾健.柴胡疏肝散对实验性肝郁证大鼠的影响[J].中药药理与临床2006,22(6)：5-6.
23.朱清静,罗欣拉,熊振芳.柴胡疏肝散对慢性束缚应激性肝郁证大鼠下丘脑-垂体-肾上腺轴的调节作用[J].湖北中医杂志,2003,25(11)：7-8.
24.陈松,李家邦,朱双罗,等.肝郁证T、B淋巴细胞活性改变及疏肝治疗影响的实验研究[J].湖南中医学院学报,2001,21(2)：7-8.
25.杨冬花,李家邦,郑爱华,等.肝气郁结证模型大鼠Thl／Th2细胞因子变化及柴胡疏肝散的干预作用[J].湖南中医学院学报,2003,23(5)：4-7.
26.陈梁,朱锦善,任建平.柴胡疏肝散对四氯化碳所致大鼠急性肝损伤的防治作用[J].中西医结合肝病杂志,2004,14(1)：42-43.
27.冯育航,董湘玉.柴胡疏肝散对应激状态下大鼠胃溃疡的治疗[J].中国现代药物应用,2007,1(10)：26-27.
28.敖海清,徐志伟,严灿.柴胡疏肝散及逍遥散对慢性心理应激大鼠血清皮质酮及胃肠激素的影响[J].中药新药与临床药理,2007,18(4)：288-291.
29.凌江红,韦连明,张钰琴.疏肝理气法对功能性消化不良大鼠下丘脑胃血浆胃泌素的影响[J].辽宁中医杂志,2009,36(10)：1812-1813.
30.吴先哲.柴胡疏肝散对心理应激大鼠行为学的影响[J].中国实验方剂学杂志,2006,12(3)：38-40.
31.凌江红,张钰琴,梁纲.疏肝理气法对夹尾应激大鼠行为学及胃组织学的影响[J].世界华人消化杂志,2009,17(3)：299-302.
32.孙占杰.加味四君子汤治疗动力障碍型功能性消化不良60例[J].山西中医,2009,25(1)：16.
33.金贤兰.四君子汤加减治疗功能性消化不良60例[J].长春中医药大学学报,2007,23(6)：33.
34.高晔.四君芍药汤治疗溃疡性结肠炎50例[J].河北中医药学报,2008,23(1)：30.
35.蔡晓静,付玉军,朱本元.加味四君子汤保留灌肠治疗溃疡性结肠炎30例[J].新中医,2009,41(60)：85-86.
36.石爱华.电热针结合四君子汤加味治疗脾胃虚寒型慢性萎缩性胃炎临床观察[J].河北中医,2009,31(3)：418-420.
37.李景花.四君子汤合丹参饮加减治疗慢性萎缩性胃炎46例[J].四川中医,2009,27(8)：89.
38.杨洁.四君子汤配合四逆散治疗肠易激综合征临床研究[J].湖北中医杂志,2009,31(7)：16-17.
39.马纯清.四君子汤合四神丸加减治疗慢性泄泻临床观察[J].光明中医,2009,24(11)：2119-2120.
40.温庆祥,古颖.四君子汤对脾虚患者免疫功能影响[J].北京中医,2006,25(4)：239-240.
41.章梅,张仲海,夏天.四君子汤对脾虚患者血清可溶性细胞粘附分子-1水平和单核细胞功能的影响[J].中国中西医结合杂志,1999,19(5)：270-272.
42.华玉淑,唐汉庆.四君子汤加减治疗老年慢性支气管炎54例[J].长春中医药大学学报,2009,25(4)：517-518.
43.郑伟鸿,郑伟达,郑东海.扶正固本法治疗恶性肿瘤经验[J].世界中西医结合杂志,2009,4(4)：292.
44.周峰,李传刚,刘用楫.四君子汤在膀胱癌治疗中的应用及研究进展[J].大连医科大学学报,2008,30(5)：473-475.
45.王海燕,朱跃科,陈煜.四君子汤防治大鼠应激性胃溃疡的初步研究[J].世界华人消化杂志,2005,13(13)：1595-1596.
46.郑小伟,宋红,包素珍,等.实验性脾气虚大鼠胃泌素的基因表达及四君子汤的干预作用[J].中华中医药杂志,2008,23(3)：264-266.
47.任平,黄熙,谢良杰.四君子汤对脾虚模型大鼠胃动素和前列腺素E2含量的影响[J].中药药理与临床,1994,6：7-8.
48.任平,黄熙,张莉.四君子汤对实验性脾虚大鼠胃排空率的影响[J].中国中西医结合杂志,2000,20(8)：596-598.
49.易崇勤,孙建宁,张家俊,等.四君子汤调整小鼠运化功能紊乱的实验研究[J].中国中西医结合杂志,1997,17(1)：42-44.
50.王洪海.四君子汤、柴疏四君汤、柴胡疏肝散作用于脾虚证大鼠模型的生物效应比较[D].北京：北京中医药大学,2007,6.
51.陈文强,黄小波,李宗信,等.四君子汤对脾虚大鼠不同脑区单胺类神经递质含量的影响[J].天津中医药,2009,26(2)：137-138.
52.李志强,陈津岩,何赞厚,等.四君子汤对脾虚证大鼠血清性激素和甲状腺激素水平的影响[J].河南中医,2008,28(3)：36-37.
53.李志强,陈津岩,何赞厚,等.四君子汤对脾虚证大鼠性激素和环核苷酸水平的影响[J].实用中医药杂志,2008,24(10)：619-620.
54.李家邦,陈松,李立新,等.四君子汤对脾虚证模型大鼠淋巴细胞功能的影响[J].成都中医药大学学报,2001,24(3)：31-32.
55.邢燕玲,游俊.四君子汤对脾气虚型慢性萎缩性胃炎大鼠外周血T淋巴细胞亚群的影响[J].湖北中医学院学报,2007,9(2)：18-19.
56.杨冬花,李家邦,郑爱华,等.脾气虚证模型大鼠Thl／Th2细胞因子的失衡以及四君子汤的干预作用[J].中国医师杂志,2004,6(2)：181-182.
57.章梅,夏天,张仲海.脾虚小鼠红细胞免疫和腹腔巨噬细胞吞噬功能改变的实验研究[J].北京中医药大学学报,1999,22(3)：26-27.
58.梁尚华,路长林,邹军,等.四君子汤对慢性应激大鼠行为学及免疫指标作 用的研究[J].成都中医药大学学报,2005,28(2)：38-40.
59.王洪海.四君子汤、柴疏四君汤、柴胡疏肝散作用于脾虚证大鼠模型的生物效应比较[D].北京：北京中医药大学,2007,6.
60.梁尚华,路长林,邹军,等.四君子汤对慢性应激大鼠行为学及免疫指标作用的研究[J].成都中医药大学学报,2005,28(2)：38-40.
61.王奇,陈云波,冯炯,等.不同治法方药对快速老化小鼠学习记忆功能的影响[J].中药药理与临床,2009,25(5)：5-7.
62.成文利,江振友,王修银,等.四君子汤及拆方对D-半乳糖诱导衰老小鼠学习记忆调节作用的影响[J].中药材,2008,31(7)：1039-1041.
63.王世荣.疏肝健脾和胃法治疗功能性消化不良疗效观察[J].吉林中医药,2008,28(6)：411-412.
64.练慧,张正利.柴胡疏肝散合四君子汤加减治疗慢性萎缩性胃炎47例[J].上海中医药杂志,2006,40(5)：27-28.
65.罗改云,马羽萍,赵玲.柴胡疏肝散合六君子汤治疗慢性乙型病毒性肝炎60例[J].陕西中医,2007,28(2)：165-167.
66.施正康.疏肝健脾法治疗胃脘痛的临床观察[J].辽宁中医杂志,2004,31(10)：831.
67.李艳彦,谢鸣,王洪海,等.肝郁脾虚证模型大鼠甲状腺轴的变化及柴疏四君汤的作用观察[J].中国中医基础医学杂志,2008,14(3)：191-195.
68.王桐生,阎玥,王玉杰,等.柴疏四君汤对肝郁脾虚大鼠下丘脑-垂体-肾上腺皮质轴变化的调整作用[J].安徽中医学院学报,2009,28(3)：29-31.
69.王玉杰,谢鸣,阎玥,等.疏肝方、健脾方、疏肝健脾方对肝郁脾虚证模型大鼠IL-2、IL-6及T淋巴细胞增殖率的影响[J].北京中医药大学学报,2009,32(6)：398-401.
1.谢鸣.“方证相关”逻辑命题及其意义[J].北京中医药大学学报,2003,26(2)：11-12.
2.肖桂林,金益强,鄢东红,等.肝郁脾虚证实验诊断指标的研究[J].湖南中医学院学报,1998,18(2)：4.
3.郑爱华,李家邦,蔡光先,等.肝气郁结证与脾气虚证的Th细胞分化中的相关性实验研究[J].中国医师杂志,2004,6(3)：357.
4.严灿,等.加减四逆散对慢性心里应激大鼠胸腺糖皮质激素受体作用的研究[J].中国中西医结合杂志,2002,22(9)：196.
5.刘建平.柴胡疏肝散合并氟西汀治疗抑郁症的临床观察[J].山西中医学院学报,2001,2(4)：31-33.
6.黄仕文.柴胡疏肝散临床应用现状[J].山西中医,2001,17(2)：74.
7.李家邦,杨冬花,蒋荣鑫,等.N F-ATc在肝气郁结、脾气虚证模型大鼠的表达以及柴胡疏肝散、四君子汤的干预作用[J].中国现代医学杂志,2005,15(10)：1515-1517.
8.李艳彦.肝郁脾虚证的模型复制及相关方剂作用的生物学基础[D].北京：北京中医药大学,2006.
9.阎玥,谢鸣,王玉杰,等.疏肝、健脾、疏肝健脾方对肝郁脾虚证模型大鼠外观表征的影响.中国科技论文在线,200906-1175.
1. 陈奇.中药药理研究方法学[M].北京：人民卫生出版社,1994,669.
2.吴圣贤,方素钦,王映辉,等.中医肝郁脾虚证症状分布和特征专家问卷调查研究[J].北京中医药大学学报,2007,30(12)：854-856.
3.曹贵东,崔志明.“解郁健脾汤”治疗34例肝郁脾虚证的临床观察[J].中医药研究,1999,15(4)：25-26.
4. 韩秋艳.肝郁脾虚证动物模型的建立[J].贵阳中医学院报,2001,23(3)：59.
5.徐叔云,卞如廉,陈修.药理实验方法学[M].2版.北京：人民卫生出版社,1991：642-643.
6.刘克嘉，邬勤娥.应激与应激性疾病[M].北京：人民军医出版社,1991：297-300.
7.岳利峰,丁杰,陈家旭,等.肝郁脾虚证大鼠模型的建立与评价[J].北京中医药大学学报,2008,31(6)：396-400.
8. 阎玥,谢鸣,王玉杰,等.疏肝、健脾、疏肝健脾方对肝郁脾虚证模型大鼠外观表征的影响.中国科技论文在线,200906-1175.
9.王阶,张兰凤,王永炎.方证对应理论源流及临床研究[J].世界科学技术.中医药现代化-基础研究,2006,6(4)：13-16.
10.张丽萍,张曼,陈友友,等.加味温胆汤对抑郁模型大鼠学习记忆能力及海马cAMP-PKA途径的影响[J].中国康复医学杂志,2008,23(12)：1082-1084.