Research On Treatment To Post-stroke Depression Under The Direction Of Theory Of "the Liver Controlling Dispersion" In Chinese Medicine

Title: Research on treatment to post-stroke depression under the direction of theory of "The liver controlling dispersion" in Chinese medicineSpecialty: Diagnostics of Chinese MedicineCandidate: Gao MinTutor: Professor Chen QunPost-stroke depression (PSD) means having depressive emotion or in the station of depression after stroke and having been confirmed by related scales. It is one of the important complications of stroke and the incidence rate is 25%-80%, mostly manifested light-midrange. The activity disorder of PSD patients can often induce the happening of depressive disorder and the last one can affect the recovery from stroke and form infernal circle. As a kind of secondary affective disorder after stroke, the PSD can step down the functional recovery of limbs and recognition, increase the case fatality ratio and affect the patients' quality of life and prognosis seriously except can cause emotional pain. At present, worker of both Chinese and western medicines have make systematical research to the pathogenesis and clinical therapy to the PSD and have make notable advancement. Making use of the Chinese medicine to treat the PSD get more and more attention and the research get more and more profound for the side-effect, addiction and contraindication of traditional and new type anti-depressive medicines (western medicines).The research approached the relationship between the theory of liver controlling dispersion and PSD. Directed by the theory of liver controlling dispersion and combined the forward research foundation, the research make use of the regulating "liver" therapy herbs-JWSNS to treat the PSA and approach the mechanism of action and provide scientific base to manufacture and develop new Chinese medicines in the future.Part One Clinical Researches1 Clinical data and Methods1.1 Research objects1.1.1 Source of the case All the 103 cases came from our capital from October, 2003 to October,2006.1.1.2 Internalization criterion(1) Patients with clear awareness, no dysgnosia and can go with examination in 2 weeks at the first post-stroking.(2) all the cases are consistent with the diagnostic criteria of brain hemorrhage and cerebral infarction which passed by the 4th national CVD academic meeting in 1995 and the stroke and depression differentiation of symptoms and signs of internal medicine of TCM, and get final diagnosis by 1～3 times skull CT or MRI.(3) Before the drug treatment, all patients have such characters: Hamilton depression rating scale (HAMD) score＞17, neurological impairment score (SSS)＞16, Barthel index＜70(Barthel index evaluation scale is used to evaluate activities of daily living(ADL))(4) Taking no anti-depression preparation in 1 weeks at the first diagnosis. Taking no monoamine oxidase inhibitor in 2 weeks and no other anti-depression preparation and antipsychotic drug. Taking no licorice root, adrenal cortex hormone, adrenocorticotrop (h)ic hormone (ACTH) or analog.(5)Normal routine of blood, urine and stool and normal function of liver and kidney, no serious medical record of heart, liver, kidney, mental disorder, epilepsy and drug allergy; Depleting innocent failure of memory of old ages, senile dementia and neurastheria before searching.1.2 Subgroup and therapy1.2.1 SubgroupAll the cases are divided into 2 groups at random in the 1st month after onset. 52 cases in the therapy group: male:32, female:20, age:38～68 years old, the mean is 40.21±8.57; 28 cases of apoplexy, 8 cases of lacunar infarction, 10 cases of cerebral embolism, 6 cases of subarachnoid hemorrhage.51 cases in control group: male:31, female:20, age:37～69 years old, the mean is 41.53±7.92,27 cases of apoplexy, 6 cases of lacunar infarction, 12 cases of cerebral embolism, 6 cases of subarachnoid hemorrhage. Before treatment, the HAMD score is 17～30, mean is 20.42±1.82/17～31, 20.16±2.51. The SSS score is 16～45, mean is (25.3±4.2)分/16～45分, 24.2±5.4. The Barthel index is 0～70, mean is (26.1±6.8)分/0～70分, 25.1±7.2. There have no statistical difference between the 2 groups in age, sex, etiological factor, course of disease, depressive degree, neurologic impairment degree and Barthel index (P＞0.05). 50 cases in healthy group, all of them came from the healthy peoples of health examination: male:30, female:20, age:36～67 years old, the mean is 40.44±8.72, and there have no statistical difference between the control group and therapy group in age and sex construction.1.2.2 Therapy and nursing methodsThe 2 groups were given orally hydergine 1mg/time, Tid. The hypertension and diabetic were given the treatment of decrease the blood pressure and blood sugar. In the same time, the technique of nerve-muscle unobstructed especially the Bobath therapy were used to train the limbs function, QD, 50min/time. In the base, the 2 groups were given the blow treating methods: the therapy group: JWSNS, composition and dosage: Bupleurum Root 5 g,White Peony Root 15g,Bitter Orange 6g,Wolfberry Fruit 15g,Capejasmine Fruit 5g,Rehmannia Root 18g,Concha haliotidis 30g. 1 dosage per day, decocted in water for oral dose and drink in the morning and evening, milkvetch root and codonopsis pilosula were added for serious deficiency of vital energy, polygoni muliflori and barbary wolfberry fruit for deficiency of kidney-essence, morindae officinalis and epimedii for deficiency of kidney-YANG, processing pinelliae and Coptis chinensis for sputum-fire, common anemarrhena rhizome and peony root bark for asthenic yin causing excessive pyrexia, flos albiziae, crude fossilia ossis mastoid and crude Ostreae testa for serious insomnia, peach seed and Carthamus tinctorius for stagnant blood. The control group: Fluoxetine (fluoxertine hydrochloride caps, lilly company, USA, Batch No208151), QD, 20mg/time and ate in the morning. Basic nursing: nursing staff communicated with the patients with broad-minded, observed the talk and behavior, perspect the mentation and strengthen the control of behavior and emotions. Affected the patients with broad-minded, evoked the interests of them and provide support, apprehension and sympathy in emotion, achieve the trust and conduct them to pour out their heart, encouraged out door activity, avoided fat and oily food and smoke and wine, drank rosae and chrysanthemi flos tea. The endemic area is calm and has light music. 4 weeks as one course of treatment and we make 2 courses of treatment. Observe and statistics the therapeutic effect. Detecting the routine of blood, urine and stool and function of liver and kidney pretherapy and the 4th and the 8th week of the cause of the therapy and scored HAMD.1.3 Index surveyed and evaluation of therapeutic effect1.3.1 Evaluation criterionReferencing Diagnostic therapeutic effect criterion of TCM diseases, which were draw up by the Nation TCM Administration in June, 1994, we institute the evaluation criterion. Excellence: symptom disappeared, normal emotion. Utility: symptom decreased, basic stabilization of emotion. Invalid: no improvement of both symptom and emotion.1.3.2 Evaluation criterion of the scaleHAMD, SSS and ADL were evaluated of the 2 groups of patients at the 4th week and 8th week of pre-treatment and post-treatment.1.3.2.1 Evaluating the depressive symptom based on HAMD scale Score 24 kinds symptoms and signs with 5 grades methods and noting the score change of the 2groups of patients pre-tretment and post-treatment. Combining the Diagnostic base, healing well (HW) and improvement criterion of clinical diseases, the results are classified into HW, excellence, utility and invalid. HW: the change of HAMD score exceed 90%; Excellence: the change of HAMD score between 90%～75%; Utility: the change of HAMD score between 75%～50%; Invalid: the change of HAMD scores below 50%.1.3.2.2 SSS score Referencing the Clinical SSS criterion of stroke patients, which was passed in the 4th CVD meeting in 1995.1.3.2.3 ADL Barthel index scoring method. Noting the score change of pre-treatment and post-treatment and assessing the effect of CVD basing on the therapeutic effect evaluation criterion of CVD. Therapeutic effect criterion is analyzed with Radit analysis and score change with t-test.2 trained doctors evaluate the Scale at the same time; therapeutic evaluation is carried out at the 4th and 8th week of pre-treatment and post-treatment.1.3.3 Detection of serum NE and 5-HT Fluorescence spectroscope, Hitachi Company. Detect serum NE and 5-HT of pre-treatment post-treatment.1.3.4 Detection of plasma cortisol collecting ulnar vein blood at 8:00AM of the subjects with calm and empty stomach station and detecting the plasma cortisol with double antibody sandwich radio-immunization.1.3.5 Detection of event-related potential P300 Evoked potential evoked potential, ampere MK15, Italy1.3.6 Station of side effect Evaluating the station of side effect with scale (TESS) at the 4th week and 8th week before the treating and in the treating course.1.4 Statistics analysis All results are expressed byx±s. The data are handled by SPSS 12.0 statistical package, in which t-test are used to group comparison, paired t-test to comparison of pre-treatment and post-treatment, X~2 test to numeration data.2 Results2.1 Comparison of clinical therapeutic effect therapy group52 examples: excellence 36 examples (69.23%), utility 6 examples (11.54%), invalid 10 examples (19.23%), total effective rate 80.77%. Control group 51 examples: excellence 27 examples (52.94%), utility 8 examples (15.69%), invalid 16 examples (31.37%), total effective rate 68.63%. There have significant difference between the therapy group and control group in total effective rate (P＜0.05), the therapy group is outstrip control group.2.2 Comparison of the scale evaluation2.2.1 Score of HAMD scale The HAMD score are coincidence between the therapy group and control group. Compared with pre-treatment, The HAMD score of the therapy group significantly decreased after taking JWSNS for 4 weeks and 8 weeks and has significant difference(P＜0.01). The score of both group decreased with the treating, which indicated that the two medicines have obviously anti-depression effect. There have significant difference between the 2 groups after treatment (P＜0.01) and the therapy group is outstrip the control group.2.2.2 SSS score The SSS score are coincidence between the therapy group and control group. Compared with pre-treatment, The SSS score of the therapy group significantly decreased after taking JWSNS for 4 weeks and 8 weeks while which of the control group didn't, which manifested that JWSNS can significantly improve the neurologic impairment.2.2.3 ADL score (Barthel index) The ADL score are coincidence between the therapy group and control group. Compared with pre-treatment, The ADL score of the therapy group significantly increased after taking JWSNS for 4 weeks and 8 weeks while which of the control group didn't, which manifested that JWSNS can improve the activities of daily living.2.3 change of NE and 5-HT in serum The levels of NE and 5-HT in serum in both 2 groups are significantly decreased before treatment comparing with normal value (P＜0.01). After the course of treatment, the levels of NE and 5-HT in serum in both 2 groups are significantly increased (P＜0.01). With the prolonged treating time, the levels of NE and 5-HT increased gradually, which indicates that the 2 kinds of medicines have effect of anti-depression. There have significant difference between the 2 groups after treatment (P＜0.01) and the therapy group is outstrip the control group.2.4 Change of plasm cortisol The levels of cortisol in both 2 groups are significantly increased before treatment comparing with normal value (P＜0.01). After the course of treatment, the levels of cortisol in both 2 groups are significantly decreased (P＜0.01) and the levels increased gradually with the prolonged treating time. There have significant difference between the 2 groups after treatment(P＜0.01) and the therapy group is outstrip the control group.2.5 Change of event-related potential P300 Compared with healthy people, the PSD patients have such characters: prolonged latent period of N2 wave and P3 wave in P300, decreased P3 wave amplitude, be different significantly from the healthy people (P＜0.01), while the other waves have no such condition (P＞0.05). After the course of treatment, the latent period of N2 wave and P3 wave in P300 shorten and P3 wave amplitude heighten of the 2 groups, there exist difference between pre-tratment and post-treatment(P＜0.05), but there have no difference between the 2 groups after treatment(P＞0.05).2.6 Side effects The side effects emerged mostly in the first 1～2 weeks of the course of treatment. There exist significant difference in the times of TESS item between the 2 groups post-treatment(P＜0.01). There have no change in Normal routine of blood, urine and stool, function of liver and kidney and electrocardiogram and creatase.3 DiscussionsJWSNS have exact effect to PSD and the total effective rate is 80.77％, which is outstripped of Fluoxetine. The effect manifests that decrease the HAMD score and SSS score, improve the neurologic impairment, increase the ADL score and improve the activities of daily living. We found that in the side effect, JWSNS have no distinct side effect and have characters of safety, prolonged and steady actions, which manifest wide prospect of clinical application. According to the result, we think the curative effect mechanism of action of JWSNS to PSD is involve in the blow: 1. Significant increase the level of serum NE and 5-HT, refrain the reuptake of monoamine neurotransmitter; 2. Decrease the plasma cortisol and regulate the function of HPA; 3. Improve the brain capacity and function of sensation and perception and execute function, increase the progress of brain to outside message and regulating function of brain to behavior.Part Two Experimental Researches1 Materials and Methods1.1 Experimental animalsWistar rats, grade SPF, male, 2 months old, 220-270g in weight. Offered by animals' centre in Southern medical university, certification no: 2002-009. the rats can drink water and take food in freedom and acclimatize for 1 week, where the light-dark cycle is 12h, temperature is 23±2℃and calm. 1.2 Experimental medicines and preparationComposition and dosage of JWSNS: Bupleurum Root 5g,White Peony Root 15 g,Bitter Orange 6 g,Wolfberry Fruit 15 g,Capejasmine Fruit 5 g,Rehmannia Root 18 g,Concha haliotidis 30 g. The herbs are bought from the first affiliated hospitalme of Guangzhou university of TCM and appraised as pure crude herbs by the drug department. Take the traditional Chinese medicine into coarse powder and soaked in eight multiple warm water for 0.5h, simmering decoction for 4h after boiled. Attention: even mixed and filtered with three-tier gauze; the 2nd and 3rd decotation with 6 multiple water for 2h. Merged the thrice physic liquor and concentrated to 1.69g/ml and preserved it in refrigerator at 4 centigrade after being cooled. Western medicine: fluoxertine hydrochloride caps(lilly company, USA, Batch No208151), dissolving 20mg fluoxertine hydrochloride caps in to 30ml distilled water and misce bene, intragastric administrating rats at a dose of 0.75mg/kg (6.25 multiple adult dosage).1.3 The main equipment and agent(omitting)1.4 The subgroupThe rats can drink water and take food in freedom and acclimatize for 1 week, where the light-dark cycle is 12h, temperature is 23±2℃and calm. Open-field test were used to sieve rats. The total score between 30～120 of level movement and vertical movement are qualified. 10 of the 80 rats are chosen as control group by SPSS 12.0 statistical package according to weight, the others are chosen to prepare Middle cerebral artery occlusion(MCAO) model and artificial operation. The living rats(remove 10 rats of artificial operation) are divided into 3 groups in random: model group, fluoxetine group and JWSNS group.1.5 Preparative method of model1.5.1 Preparation of rat MCAO model with electric coagulation1.5.2 Complex preparation of rat PSD model Shift the MCAO rats in mouse cages after awake and breed alone for 28days. In the 8th days after stroke(neurological impairment have recover on the whole), 9 kinds of mild and unpredictable stress stimulus will be given for 21 days.1.6 Index and methods1.6.1 Common conditionObserve the mind, food taking and drinking water conditions, the stool texture, whether have infected and died rats, note the time of death and find out the death cause by dead body dissection, measure the weight every week. 1.6.2 SSS score of focal cerebral ischemia rats Longa5 is used to score the SSS after the rats awake in 24h.1.6.3 Observation of rats ethology1.6.3.1 The Sucrose Consumptions test The test are preceding in the 28th days after stroke. First, the rats are trained to drink 1％cane sugar solution, which means in the first 48h 1％cane sugar solution are used to take the place of the tap water, then giving 1％cane sugar solution to rats and calculating the drinking weight of 24h.1.6.3.2 Open-field test1.6.4 Detection of the monoamine transmitter(NE,5-HT,DA) of rat' brain Fluorospectrophotometry. Calculation the concrete contents of NE, 5-HT and DA: (values of the sample tube A—values of the vacant tube A)/(values of the standard A—values of the vacant tube A)×0.2×1.5×(1/weight of the brain tissue g)=( )U/g。1.6.5 Detection of the contents of cAMP, the activity of PKA and PKC of rat'hippocampus Detection of the contents of cAMP: radio-immunity method. Detection of the activity of PKA and PKC: radio active isotope method.1.6.6 Detection of the expression of P-CREB in rat'hippoeampus Analyzing and statistics optical density and areas density of expression of P-CREB with immunohistochemical method and patho-image analytical system.1.7 The administrating dosage and methodsThe time of the administration is 22d, ltime/d of intragastric administration from the 8th day after stroke and measure weight 1 time/week. The control group, model group and artificial operation group are given the same volume of distilled water. The dosage of fluoxertine hydrochloride group is 0.75mg/kg and JWSNS group 3.38 g/d to 1 rat.1.8 Statistical treatment All results are expressed by (?)±s. The data are handled by SPSS 12.0 statistical package. ANOVE are used to group comparison, in which LSD are to regular variance and Dunnett'sT3 for irregular variance. Non-parameter test are used to data with no normal distribution. Paired t-test is used to group comparison of mean.2 Results2.1 Model and death conditions of rats 12 rats died in 4 weeks after the operation: 5 died in the course of the operation, 3 died for hemorrhoea, 2for anesthetic accident and 2 died in the course of the complex model. 2 died in 7 days of stress process: 1 died for electro-stress and 1 have no exact reason. After the stress process finished, 5 died before executing: 3 for mal-intragastric administration and 2 for pulmonary infection. 1 died of the control group and none of artificial operation group. 5 died in the 64 rats which are used to make model of MCAO, 2 scored 0 in SSS, the achievement ratio of making model is 82.3％. 51 rats succeeded in making model the achievement ratio is 79.7％.2.2 SSS score of operation rats All the MCAO rats show the left neurological impairment of different degree and the score is 2.61±0.59 except 2 rats after awake. There have no neurological impairment in artificial operation group.2.3 Change of rats weight Compared with the control group, the other groups manifested weight increased, but the difference were not distinct; the weight of the model group, fluoxetine group and JWSNS group lower significantly than the control group between the 14th day to 28th day after stroke(P＜0.05 or 0.01), but there had no difference between the artificial operation group and the control group(P＜0.05). In addition, the rats weight in model group increased slowly while those treatment groups had the tendency of increase weight. The results manifested that complex model preparation can significant step down the weight growth, while those treatment groups have the adverse effect and the difference is significantly comparing to the model group.2.4 Results of the rats ethnology2.4.1 Results of the sucrose Consumptions test The sucrose consumption significantly decreased in model group, artificial operation group and the treatment groups compared with that in the control group (P＜0.05 or 0.01). The sucrose consumption significant increased in the treatment group compared with that in the model group (P＜0.05 or 0.01). Complex model preparation can significantly decrease the sucrose consumption, while the treatment groups can improve the condition which indicates that the medicines can depress the PSD rat's interest and the occurrence of depressive action.2.4.2 Results of the open-field test Compared with the control group, the model group and the treatment groups manifested that the movement of level decreased significantly in the 7th day after the stroke (P＜0.05) but the vertical movement didn't change. The level and vertical movement decreased significantly in the 14th, the 21st and 28th day after stroke of the model group, artificial operation group and the treatment groups (P＜0.05 or 0.01). Compared with the model group, there's no difference of the vertical movement in the 7th day after stroke but have significant difference of the level and vertical movement in the 14th day of artificial operation group and level movement of JWSNS group(P＜0.05). In the 21st day and 28th the both movement significantly increased of the artificial operation group and the treatment groups(P＜0.05 or 0.01). In addition, the open-field test didn't change of the control group but the movement decreased in the operation rats 1 week later and the rats in the treatment groups manifested the tendency of descend first and ascend last. Conclusion: Complex model preparation can make the open-field behavior disorder(decrease the level and vertical movement), which indicate that probe behavior and spontaneous movement decreased, while the treatment groups can significantly improve the disorder.2.5 Result of the monoamine transmitter of rats' brain2.5.1 Result of the NE of rats' brain Compared with the control group, the model group and the treatment groups manifested that the NE decreased significantly in the left and right cortex of forehead and brain stem(P＜0.05 or 0.01). Compared with the model group, the artificial operation group and the treatment groups manifested that the NE increased significantly in the left and right cortex of forehead and brain stem (P＜0.05 or 0.01). Results indicate that complex model preparation can make the NE decreased while the medicines can improve the change.2.5.2 Result of the 5-HT of rats' brain Compared with the control group, the model group and the treatment groups manifested that the 5-HT decreased significantly in the left and right cortex of forehead and brain stem (P＜0.05 or 0.01) and the artificial operation group decreased also but have no statistical meanings. Compared with the model group, the artificial operation group and the treatment groups manifested that the 5-HT increased significantly in the left and right cortex of forehead and brain stem(P＜0.05 or 0.01). Results indicate that complex model preparation can make the 5-HT decreased while the medicines can improve the change.2.5.3 Result of the DA of rats' brain Compared with the control group, the model group and the treatment groups manifested that the DA decreased significantly in the left and right cortex of forehead(P＜0.05 or 0.01). Compared with the model group, the artificial operation group and the fluoxetine group manifested that the DA increased significantly in the right cortex of forehead(P＜0.05) and the fluoxetine group manifested that the DA increased significantly in the brain item(P＜0.05); the JWSNS group manifested that the DA increased significantly in the right cortex of forehead and the brain item(P＜0.05). Results indicate that complex model preparation can make the DA decreased while the medicines can improve the change. 2.6 Result of the cAMP contents and activity of PKA and PKC in rats' hippocampus Compared with the control group, the model group and the artificial operation group manifested that the cAMP contents decreased significantly (P＜0.01) and the fluoxetine group and the JWSNS group manifested that the cAMP contents increased significantly in the cortex and hippocampus (P＜0.01) and there's no difference between the 2 treatment groups. Compared with the control group, the model group and the artificial operation group manifested that the activity of PKA decreased significantly in the cortex and hippocampus (P＜0.05) and the fluoxetine group and the JWSNS group manifested that the activity of PKA increased significantly in the cortex and hippocampus (P＜0.05) and there's no difference between the 2 treatment groups. Compared with the control group, the model group and the artificial operation group manifested that the activity of PKC increased significantly (P＜0.01)and the fluoxetine group and the JWSNS group manifested that the activity of PKC decreased significantly in the cortex and hippocampus (P＜0.01) and there's no difference between the 2 treatment groups.2.7 Result of the P-CREB expression in rats' hippocampus The P-CREB expression is broad in the normal rats hippocampus and in the CA1 realm, the expression mostly lie in nuclear of the pyramidal layer the color is deep brown and some expression lie in the kytoplasm and ecphyma but the color is faint. In the model group and artificial operation group, the masculine cells are fewer and show vacuolus or atrophia and faint color, the area density and light density are lower (P＜0.05 or 0.01), while the 2 treatment groups have the opposite manifestation (P＜0.05)5 DiscussionsThe results indicate that the complex model preparation can significantly decrease the growth of weight, so the slowly weight growth is one of the manifestation of PSD rats. Fluoxetine and JWSNS can increase the weight and super than the model group in the 28th day after stroke. The results of the sucrose consumption test indicate that the sucrose consumption significantly decreased in PSD rats and the fluoxetine and JWSNS can improve the condition (P＜0.05 or 0.01), which indicate that the medicines can depress the PSD rats interest and the occurrence of depressive action. The results of the open-field test indicate that the complex model preparation can make the open-field behavior disorder (decrease the level and vertical movement), which indicate that probe behavior and spontaneous movement decreased, while the 2 kinds of medicines can significantly improve the disorder. Compared with the control group, the contents of NE, 5-HT and DA significantly decreased in model group in the left and right cortex of forehead and brain stem (P＜0.05 or 0.01), maybe this is related to the lessen cortical neuron transmitter synthesis induced by the stroke injury the projection fibers of NE, 5-HT and DA to cerebral cortex., while the 2 kinds of medicines can significantly improve the tendency (P＜0.05 or 0.01). The model group manifested that the cAMP contents and the activity of PKA decreased significantly (P＜0.01) while the activity of PKC increased which indicate that the cAMP-PKA signal iter system down regulated and the PKC up regulated in PSD rats, the 2 kinds of medicines have the effect of improve and regulate the second messenger and protien kinase, which indicate that the depressive effect of the medicines maybe related to the regulation of acceptor of cAMP-PKA and PKC signal iters. The PSD rats showed the P-CREB expression decreased in cortex and hippocampus, the mechanism maybe is that cAMP-PKA signal iter can directly make the CREB ptiosphorylation and activation. There exist neuronal functional impairment in PSD rats, for which the monoamine transmitter receptor and the cAMP-PKA signal iter have functional impairment, which induced the downregulation of CREB function. The intervention of the 2 kinds of medicines to PSD are related to the increased expression of CREB, but the concrete effective routes are still need to be probed in the late research.Part Three Conclusions1. Making use of the regulating "liver" therapy herbs-JWSNS to prevent and cure the PSA have scientific theoretical base directed by the theory of liver controlling dispersion.2. JWSNS have exact effect to PSD and the total effective rate is 80.77%, which is outstripped of Fluoxetine. The effect manifests that decrease the HAMD score and SSS score, improve the neurological impairment, increase the ADL score and improve the activities of daily living. We found that in the side effect, JWSNS have no distinct side effect and have characters of safety, prolonged and steady actions, which manifest wide prospect of clinical application. According to the result, we think the curative effect mechanism of action of JWSNS to PSD is involve in the blow: 1. Significant increase the level of serum NE and 5-HT, refrain the reuptake of monoamine neurotransmitter; 2. Decrease the plasma cortisol and regulate the function of HPA; 3. Improve the brain capacity and function of sensation and perception and execute function, increase the progress of brain to outside message and regulating function of brain to behavior.3. JWSNS can significantly increase the sucrose consumption of PSD rats and depress the interest and the occurrence of depressive action and improve the probe behavior and spontaneous movement. JWSNS can significantly increase the contents of NE, 5-HT and DA and improve and regulate the second messenger and protien kinase, which indicate that the depressive effect maybe related to the regulation of acceptor of cAMP-PKA and PKC signal iters. In addition, the intervention of JWSNS to PSD is related to the increased expression of CREB.