Objective To investigate the patterns of syndrome changes and their possible material basis in mouse models of chronic psychological stress during the modeling process.Methods A chronic unpredictable mild stress(CUMS)method was employed to prepare a model of chronic psychological stress in mice.After 2 weeks of modeling,Xiaoyao powder(XYS group)and Sini powder(SNS group)were administered concurrently with the modeling process.General conditions,behavioral,and biochemical indicators were compared between the modeling mice(M4 and M6 group)and the mice treated for 2 weeks(S4 and X4 group)and 4 weeks(S6 and X6 group)after chronic psychological stress.Results Compared with M4 group mice,body mass,total distance and central distance in the open field test,serum NE concentration,and gastric Ghrelin expression were increased in S4 group and X4 group mice,and sugar water preference rate and serum D-xylose concentration were increased in S4 group mice.Compared with X4 group mice,total distance in the open field test and serum D-xylose concentration were increased in the S4 group mice.Compared with M6 group mice,body mass,serum NE concentration,serum D-xylose concentration,and gastric Ghrelin expression were increased in group S6 and X6 group mice;sugar water preference rate,total distance in the open field test,and active avoidance counts in the shuttle box test were increased in X6 group mice,while their serum CORT concentration was decreased.Compared with S6 group mice,body mass,total distance in the open field test,serum D-xylose concentration,and gastric Ghrelin expression in X6 group mice were increased.Conclusions During the process of modeling chronic psychological stress in mice,the traditional Chinese medicine syndrome evolved from liver qi stagnation to liver qi stagnation with spleen deficiency.The biological bases of the syndrome changes may be the combined changes in serum CORT and NE concentrations and the decrease in gastric Ghrelin levels.

The development of bio-psycho-social medical models has focused attention on the impact of chronic psychological stress on diseases.Chronic psychological stress falls within the category of emotional etiology in traditional Chinese medicine.This paper systematically reviews research progress into the chronic psychological stress-related combination of disease and syndrome,and analyzes the advantages and limitations of different models.We also provide insights into the direction and improvements of future research into chronic psychological stress-related disease pattern models.

Objective To investigate the patterns of syndrome changes and their possible material basis in mouse models of chronic psychological stress during the modeling process.Methods A chronic unpredictable mild stress(CUMS)method was employed to prepare a model of chronic psychological stress in mice.After 2 weeks of modeling,Xiaoyao powder(XYS group)and Sini powder(SNS group)were administered concurrently with the modeling process.General conditions,behavioral,and biochemical indicators were compared between the modeling mice(M4 and M6 group)and the mice treated for 2 weeks(S4 and X4 group)and 4 weeks(S6 and X6 group)after chronic psychological stress.Results Compared with M4 group mice,body mass,total distance and central distance in the open field test,serum NE concentration,and gastric Ghrelin expression were increased in S4 group and X4 group mice,and sugar water preference rate and serum D-xylose concentration were increased in S4 group mice.Compared with X4 group mice,total distance in the open field test and serum D-xylose concentration were increased in the S4 group mice.Compared with M6 group mice,body mass,serum NE concentration,serum D-xylose concentration,and gastric Ghrelin expression were increased in group S6 and X6 group mice;sugar water preference rate,total distance in the open field test,and active avoidance counts in the shuttle box test were increased in X6 group mice,while their serum CORT concentration was decreased.Compared with S6 group mice,body mass,total distance in the open field test,serum D-xylose concentration,and gastric Ghrelin expression in X6 group mice were increased.Conclusions During the process of modeling chronic psychological stress in mice,the traditional Chinese medicine syndrome evolved from liver qi stagnation to liver qi stagnation with spleen deficiency.The biological bases of the syndrome changes may be the combined changes in serum CORT and NE concentrations and the decrease in gastric Ghrelin levels.

The development of bio-psycho-social medical models has focused attention on the impact of chronic psychological stress on diseases.Chronic psychological stress falls within the category of emotional etiology in traditional Chinese medicine.This paper systematically reviews research progress into the chronic psychological stress-related combination of disease and syndrome,and analyzes the advantages and limitations of different models.We also provide insights into the direction and improvements of future research into chronic psychological stress-related disease pattern models.

Objective To observe the effects of stress treatment for different time on autonomic behaviors and spatial learning-memory abilities of rats and to investigate the therapeutic efficacy of Chaihu Shugan San(CSS). Methods Seventy-five 8-week-old Wistar rats were randomly divided into blank control group, model control group, and low-, middle-, and high- dose CSS groups, 15 rats in each group. Chronic multi-stress model was set up. The rat body weight in various groups was measured. The autonomic behaviors of rats were observed by open field test, and the abilities of spatial learning-memory of rats were examined by Morris water maze test. Results (1)On modeling day 20, 30, the model control group had lighter body weight than the blank control group (P < 0.01); the middle-, high- dose CSS groups had higher body weight than the model control group (P < 0.05 or P < 0.01) , and the high-dose CSS group had the highest body weight, the difference being insignificant compared with the blank control group (P > 0.05). (2)Open field test results showed as follows:Compared with the blank control group, the total distance and central-area distance were shortened (P < 0.01) and the average speed was decreased(P < 0.01) in the model control group at different modeling time points, the effect being positively correlated with the modeling time; compared with the model control group, the total distance and central-area distance were prolonged(P < 0.05 or P < 0.01) and the average speed was increased (P < 0.05 or P < 0.01) in the low-, middle-, and high- dose CSS groups at different modeling time points, and the therapeutic efficacy of high- dose CSS group was approach to the blank control group. (3)Morris water maze test results showed as follows: Compared with blank control group, the average latent period was prolonged and the times of platform crossing were decreased in the model control group (P < 0.01); compared with the model control group, the average potential time was shortened and the times of platform crossing were increased in the middle- and high-dose CSS groups (P<0.01), the efficacy being not significantly different from that of the blank control group (P > 0.05). Conclusion The chronic stress may decrease the excitability, reduce autonomic behaviors, and injure spatial learning and memory abilities of rats, the effect being positively correlated with the modeling time. And CSS has an effect on improving the above indexes, in particular the middle-and high-dose of CSS.

Objective To observe the effects of kidney-tonifying therapy on spatial learning, memory abilities and ultrastructure of hippocampal dentate gyrus ( DG ) cells of kidney deficiency rats induced by sexual intemperance. Methods SD rats with low reproductive capacity were caused by continuously mating for 6 months, and then were randomly divided into 5 groups, namely model group, low- and high-dose of Liuwei Dihuang pills (LDP) groups (in the dosage of 4.8, 9.6 g·kg-1·d-1), low-and high-dose of Jingui Shenqi pills (JSP) group (in the dosage of 5.2, 10.4 g·kg-1·d-1), 8 rats in each group. Except the model group, the other groups were respectively given with the corresponding medication. SD rats aged 2 months served as the normal control group. After treatment for 30 continuous days, the learning and memory abilities of rats were examined by Morris Water Maze. The cell ultra structure of hippocampal dentate gyrus was observed by transmission electron microscopy. Results The results of the place navigation test of Morris water maze showed that the escape latency of rats was prolonged obviously in the model group compared with that of the normal control group (P<0.01), and the escape latency of rats in the medication groups was shorter than the kidney deficiency model group (P<0.05 or P<0.01). The results of spatial probe test showed that the residence time in the former hidden platform quadrant and its surrounding area was significantly shortened in the model group compared with that of the normal control group ( P<0.01) , but was prolonged after medication of high-dose JSP ( P<0.05 or P<0.01 compared with that of the model group). Under the electron microscope, the cell ultra structure lesions of hippocampal dentate gyrus were much relieved in the high-dose LDP group, and high-dose JSP group as compared with those of the model group. Conclusion ( 1) Long-term sexual intemperance can impair spatial learning and memory abilities and causes the cell ultra structure lesions of hippocampal dentate gyrus of rats. (2) The kidney-tonifying therapy can significantly alleviate the spatial learning and memory disturbance and the cell ultra structure lesions of hippocampal dentate gyrus induced by sexual intemperance. ( 3) There are not significant differences between the two kidney-tonifying therapies in improving spatial learning and relieving cell ultra structure lesions. The effect of JSP on improving spatial memory abilities is better than that of LDP.

Objective To investigate the effects of Xiao Yao San on intracellular Ca2 + concentration in cultured rat hippocampal neurons in the state of chronic stress and study the mechanism of chronic stress injuring and XiaoYao San protecting. Methods MK-801 acts as tool,cultured rat hippocampal neurons were divided into seven groups, those were group 1 (control), group 2 (normal serum), group 3 (normal serum + Glu), group 4 (model serum + Glu), group 5 (model serum + Glu + MK-801), group 6 (Xiaoyaosan + Glu), group 7 (Xiaoyaosan + Glu + MK-801). to detect intracellular Ca2+ concentration in cultured hippocampal neurons in the simulated micro - environment of chronic stress and after intervention with the serum treated with Xiao Yao San by confocal laser microscope at the same period of time. Results Compared with group 1 (779.97 ± 36.81), concentration of Ca2+ intracellular of group 2 (1092.38 ± 36.41), group 3 (1472.49 ± 76. 19), group 4 (1509.52 ±104.69) and group 5 (1186.97 ±41.92) all increased significantly (P＜0.01) ,group 6 (908.74 ±40.24) increased too (P ＜ 0.05), compared with group 2, concentration of Ca2 + intracellular of group 3,4 and 5 all increased significantly (P ＜ 0.01), but group 7 (721.99 ± 60.33) decreased significantly (P ＜ 0.01). Compared with group 4, concentration of Ca2+ intracellular of group 6 and 7 decreased significantly (P＜ 0.01), group 5 decreased too (P ＜ 0.05), compared with group 6, concentration of Ca2 + intracellular of group 5 increased significantly (P ＜ 0.01),when group 7 decreased significantly (P＜0.01). Conclusion Serum of chronic stress treated with Xiao Yao San has the effect of inhibiting Ca2+ overload in hippocampal neurons,it may work through a variety of signaling pathways including Glu-NR-Ca2+ to maintain the steady-state of Ca2+ concentration in hippocampal neurons, and then to protect neurons from the neurotoxic effects of excitatory.

Objective To observe the mechanisms that Xiaoyao powder influences the hypothalamus-pituitary-adrenal (HPA) axis of chronic-stress rats. Methods Chronic stress rats were as researching object,and RU-38486 acted as tool drugs. The serum-GC density of rats were tested with ELISA,and the glucocortcoid(GR) in hippocampus neuron were tested with immunofluorescence,the CRH mRNA in hypothalamus were tested by in situ hybridization (ISH). Results Compared with normal group ( 1.09 ± 0.11 ;0.57 ± 0.10), the expression of GR in hippocampus of model group decreased(0.65 ± 0. 10; P ＜ 0. 01 ), and the expression of CRH mRNA in hypothalamus of model group increased ( 1.12 ±0. 11; P＜0. 0l ) ,the GR in hippocampus of RU-38486 group increased ( 1.59 ± 0. 11; P ＜ 0. 01 ), and the expression of CRH mRNA in hypothalamus of RU-38486 group reduced (0.48±0.10; P＜0.05) ,but both the expression of GR in hippocampus and the CRH mRNA in hypothalamus of Xiaoyao powder group were no change (0.62 ±0.08;0.97 ±0.13; P＞0.05). Compared with model group,both the expression of GR in hippocampus of RU-38486 and Xiaoyao powder group increased (P＜0. 01) ,and both the expression of CRH mRNA in hypothalamus of RU-38486 and Xiaoyao powder group reduced (P＜0.01). Conclusion Multi-stress can result in the expression of GR in hippocampus of rats decreasing and the expression of CRH mRNA in hypothalamus increasing, but those changes can be restrained by Xiaoyao powder, and it is the maybe mechanism of Xiaoyao Powder resisting chronic stress in HPA axis.

[Objective] To observe the influence of Xiaoyao Powder on the concentration of Ca2+ in hippocampal synaptosome of multi - stress model rats.[Methods] Wistar rats were randomly allocated to five groups: normal control (Group A) , model 1 (Group B), Xiaoyao Powder 1 (Group C), model 2 (Group D), and Xiaoyao Powder 2 (Group E) . All the rats except those of Group A were replicated to chronic multi-stress models. At the meantime, Groups C andE were given the decoction of Xiaoyao Powder, 1.06g each for 21 days and 42 days respectively. Groups A, B and D were administered by gavage the equal amount of normal saline. After the administration, the hippocampal homogenate was taken to detect the concentration of hippocampal synaptic Ca2+ by fluorimetry. [Results] Compared with Group A, the concentration of Ca2+ in hippocampal synaptosome of Groups B and C was increased, having significant difference ( P

Objective To observe the content changes of corticosterone and gastrointestinal hormones in serum of chronic multi-stress rats and to investigate the effect of Xiaoyao Powder and Chaihu Shugan Powder.Methods Wistar rats were randomly allocated to four groups:normal group(group A),model group(group B),Xiaoyao Powder group(group C),Chaihu Shugan Powder group(group D)etc.Chronic multi-sress models were established in all the rats except those of normal group.Xiaoyao Powder group and Chaihu Shugan Powder group were respectively given the corresponding drugs for 21 days.Normal group and model group were administered the equal amount of normal saline by gavage.After the administration,the open-field test was used to observe the behavior changes of the rats,and the radioimmunoassay method was adopted to detect the serum corticosterone and gastrin contents and plasma motilin level.Results Compared with the normal group,the body weight of model group was decreased(P