Study on regulatory mechanism of compatibility of ginseng and gecko dispensing granule on neuroendocrine immune network in model rats with kidney yang deficiency / 中国药房

OBJECTIVE To explore the regulatory mechanism of compatibility of ginseng and gecko dispensing granule on kidney yang deficiency model rats. METHODS Male SD rats were randomly divided into normal group （no modeling ，no administration），model group （modeling，no administration ），Jinkui shenqi pill group （modeling，dose of 2.33 g/kg），ginseng group（modeling，dose of 0.53 g/kg），gecko group （modeling，dose of 0.21 g/kg）and compatibility group （modeling，ginseng 0.53 g/kg and gecko 0.21 g/kg）. The body mass and anal temperature of rats were measured at different time points ；the serum levels of cAMP ，cGMP，CRH，ACTH，CORT，T，T3，T4，E2，IgG and IgM were measured ；the pathomorphological changes of adrenal gland ，thyroid gland and testis were observed ；mRNA expression of CRH ，thyroid stimulating hormone releasing hormone （TRH）and gonadotropin releasing hormone （GnRH）in hypothalamus were detected. RESULTS Compared with model group ，the anal temperature ，the levels of cAMP ，CRH，ACTH，CORT，T3，T and cAMP/cGMP ，T/E2 in serum and mRNA expressions of TRH and GnRH in hypothalamus were significantly increased in the compatibility group （P＜0.05 or P＜0.01）；the levels of cGMP，E2 and IgG in serum and mRNA expression of CRH in hypothalamus decreased significantly （P＜0.05 or P＜0.01）； the pathological injuries of adrenal gland ，thyroid gland and testis were all improved. Compared with ginseng or gecko dispensing granules alone ，the anal temperature and T/E 2 of rats in the compatibility group increased significantly ，and mRNA expression of CRH in hypothalamus decreasedsignificantly （P＜0.05 or P＜0.01）. CONCLUSIONS Thecompatibility of ginseng and gecko dispensing granule has a synergistic regulatory effect on kidney yang deficiency model rats ， the mechanism of which may be associated with hypothalamus-pituitary-adrenal axis ， hypothalamus-pituitary-thyroid axis ， hypothalamus-pituitary-gonad axis and neuroendocrine immune network formed by immune function. Compatible drugs are better than single drugs.

Association between polymorphism of hypothalamus-pituitary-adrenal-axis related genes and attempted suicide in patients with depression and its interaction with environmental factors / 中华行为医学与脑科学杂志

Objective:To investigate the association between the polymorphisms of the hypothalamus pituitary adrenal axis related genes SKA2, AVPR1B, CRHR2 and suicide attempts in patients with depression, and the interaction between the genes and environmental factors.Methods:From March 2017 to August 2018, sixty-one patients with depression who were hospitalized for suicide were selected (case group), and 57 subjects matched with the age, gender and education level of the case group (control group) were selected in the same period.Snapshot genotyping technique was used to test the genotypes of case group and control group.Barratt impulsivity scale (BIS-Ⅱ) and life event scale (LES) were used to assess the impulsive traits and mental stress of individuals in the past year.Chi-square test and independent sample t-test were used for inter group comparison by SPSS 22.0 software.Gene-environment interaction was analyzed by the generalized multi factor dimensionality reduction. Results:The total scores of BIS-Ⅱ and LES in case group(65.05± 11.14, 34.16±27.23) were higher than those in the control group (53.30 ± 9.07, 11.67±12.64), the differences were statistically significant (both P<0.05). There was no significant difference in gene frequency and allele frequency of SKA2 and CRHR2 between the two groups ( P>0.05). The genotype frequency and allele frequency of rs28373064 of AVPR1B gene were significantly different between the two groups (χ 2=5.763, 4.279, both P<0.05), but there was no significant difference after Bonferroni correction ( P>0.05). The best interaction model in GMDR was the third-order model constructed by rs28373064 of AVPR1B gene, impulsive traits and life events, with the highest accuracy of 0.789 for sample test( P=0.001). In multiple genetic models, rs28373064 of AVPR1B gene was associated with attempted suicide behavior in patients with depression(dominant model: A/G-G/G ( OR=0.38, 95% CI=0.16-0.88, P=0.021), overdominant model: A/G ( OR=0.36, 95% CI=0.15-0.87, P=0.019), log-additive model: A/A, A/G and G/G ( OR=0.44, 95% CI=0.20-0.96, P=0.034)). Conclusion:rs28373064 polymorphism of AVPR1B gene is associated with attempted suicide behavior in patients with depression.AA genotype carriers of AVPR1B gene are more likely to commit suicide under the influence of life events and impulsive.

Regulatory Effect of Polygala tenuifolia and Licorice-simmered P. tenuifolia on Learning and Memory， HPA Axis Function and Neurotransmitters in Rats with Heart-kidney Imbalance Insomnia / 中国实验方剂学杂志

Objective:To compare the regulatory effects of <italic>Polygala tenuifolia</italic> and licorice-simmered <italic>P. tenuifolia</italic> on learning and memory， hypothalamus-pituitary-adrenal axis （HPA axis） function and neurotransmitters in rats with heart-kidney imbalance insomnia. Method:The rat model of insomnia induced by multi-factor stimulation was established. After the model being made， the administration groups were given the extracts of <italic>P. tenuifolia</italic> and licorice-simmered <italic>P. tenuifolia</italic> by gavage （dose of 8 g·kg^-1·d^-1）， while the normal group and model group were given the same volume of normal saline for 7 days. Morris water maze was used to detect the changes of learning and memory ability of rats in each group. Enzyme-linked immunosorbent assay （ELISA） was used to determine the levels of corticotropin-releasing hormone （CRH）， adrenocorticotropic hormone （ACTH） and cortisol （CORT） in serum of rats from each group. The contents of 5-hydroxytryptamine （5-HT）， dopamine （DA）， <italic>γ</italic>-aminobutyric acid （GABA） and glutamic acid （Glu） in the hypothalamus of rats were determined simultaneously by ultra performance liquid chromatography tandem mass spectrometry （UPLC-MS/MS）. Result:Compared with the normal group， the spatial learning and memory ability of rats in the model group<italic> </italic>was decreased， the times and time of staying in target quadrant were significantly reduced （<italic>P<</italic>0.05， <italic>P<</italic>0.01）， the levels of CORT， CRH and ACTH in serum were significantly increased （<italic>P<</italic>0.01）， the contents of GABA， DA， 5-HT in hypothalamus tissue were significantly decreased （<italic>P<</italic>0.01）， and the content of Glu was significantly increased （<italic>P<</italic>0.01）. Compared with the model group， the spatial learning and memory ability of rats in the <italic>P. tenuifolia</italic> group and licorice-simmered <italic>P. tenuifolia </italic>group<italic> </italic>were increased， the times and time of staying in the target quadrant were significantly increased （<italic>P<</italic>0.05， <italic>P<</italic>0.01）， the levels of CORT， CRH and ACTH in serum were significantly decreased （<italic>P<</italic>0.05， <italic>P<</italic>0.01）， the contents of GABA， DA and 5-HT in hypothalamus tissue were significantly increased （<italic>P<</italic>0.05， <italic>P<</italic>0.01）， and the content of Glu was significantly decreased （<italic>P<</italic>0.05）. The recovery degree of each index in the licorice-simmered <italic>P. tenuifolia</italic> group was better than that in the <italic>P. tenuifolia</italic> group. Conclusion:Both <italic>P. tenuifolia</italic> and licorice-simmered <italic>P. tenuifolia</italic> can improve the learning and memory ability， improve the function of HPA axis， regulate the level of central neurotransmitters， and have the effect of calming the mind and improving the intelligence of rats with heart-kidney imbalance insomnia. The effect of licorice-simmered <italic>P. tenuifolia</italic> is better than that of <italic>P. tenuifolia.</italic>

Evaluación de la funcionalidad del eje hipotálamo-hipófiso-adrenal a través del test de respuesta del cortisol al despertar en pacientes con diabetes mellitus tipo 1 con y sin depresión: Estudio Multicéntrico Argentino (EMA-1) / Evaluation of the hypothalamo-pituitary-adrenal axis using the cortisol awakening response test in patients with type 1 diabetes mellitus with and without depression: Multicenter Argentine Study (EMA-1)

Introducción: la depresión (DP) tiene una alta prevalencia en pacientes con diabetes mellitus tipo 1 (DM1) y se asocia a repercusiones clínicas negativas como mayor morbimortalidad cardiovascular y complicaciones crónicas. Existen pocos estudios publicados sobre la funcionalidad del eje hipotálamo-hipófiso-adrenal (H-H-A) en DM1 con DP, y la relación entre la DP y el test de respuesta del cortisol al despertar (RCD) con el control glucémico (CG). Objetivos: analizar la funcionalidad del eje H-H-A a través de la evaluación del RCD en pacientes con DM1 (PD1) con y sin DP. Como objetivos secundarios, conocer la prevalencia de DP en PD1 y ver si existe relación entre el RCD y CG, y entre DP y CG. Materiales y métodos: estudio observacional, prospectivo, de corte transversal, multicéntrico, nacional. Se incluyeron PD1 mayores de 18 años; se utilizó cuestionario Patient Health Questionnaire-9 (PHQ-9) para diagnóstico de DP. Se tomaron muestras de cortisol salival al despertar y a los 30 minutos (RCD), y se consideró RCD bloqueado si el valor de cortisol de los 30 minutos no aumentaba más del 50% del basal. Además se tomaron muestras de sangre en ayunas para medir glucemia, fructosamina y HbA1c. Resultados: se incluyeron 79 pacientes, 39% hombres, edad promedio 38±15 años, duración de la diabetes de 16±13 años; 53% casados/en pareja y 87% con ingresos económicos estables. El 68% de los PD1 presentó el RCD bloqueado. En PD1 con DP el 85% presentó el RCD bloqueado vs el 60% en los no deprimidos y dicha diferencia fue marginalmente significativa (p=0,05). La prevalencia de DP fue de 39%. No se encontró ninguna relación significativa entre RCD bloqueado y control glucémico (p>0,05). Los PD1 con DP moderada-severa presentaron un peor control glucémico en relación a los PD1 sin depresión (evaluado por glucemia mayor de 120 mg/dl, fructosamina mayor de 285 umol/l; p<0,05) y la relación no fue significativa para HbA1c aunque mostró una tendencia. Conclusiones: en pacientes con DM1 y DP se halló el RCD bloqueado en un alto porcentaje. Dado que la DP se asocia a mayor morbimortalidad cardiovascular, podría utilizarse el test de RCD como biomarcador de DP, y podría servir para estratificar esta sub-población de alto de riesgo. La depresión moderada-severa se asoció a peor control glucémico, por lo tanto, diagnosticar y tratar adecuadamente la DP en PD1 podría contribuir a prevenir la aparición o progresión de complicaciones crónicas.

Introduction: depression (DP) has a high prevalence in patients with type 1 diabetes mellitus (DM1) and is associated with negative clinicals consequences like more cardiovascular morbimortality and chronic complications. There are few studies published about the dysregulation of hypothalamopituitary-adrenal axis (H-P-A) in DM1 with DP and the relation between DP and the Cortisol Awakening Response Test (CAR) with the glycemic control (GC). Objectives: examine the functionality of the H-P-A axis using the Cortisol Awakening Response Test (CAR), in patients with DM1 (PD1) with and without DP. Determine the prevalence of DP in PD1 and examine if there is any relation between CAR and GC and DP and poorer GC. Materials and methods: observational, prospective, national, multicenter study. Patients with DM1, older than 18 years old; Patient Health-9 questionnaire (PHQ-9) was used to diagnose DP and 2 samples of salivary cortisol, and blood samples for glycemia, glycated albumin and Hba1c. Results: 79 patients with DM1 (PD1) were included, 39% male, mean age 38± 15 years old, an average of 16±13 years evolution of diabetes; 53 % married/couple and 87 % have a regular incomes. 68% of PD1 presented CAR blunted. In PD1 with DP 85% has CAR blunted versus 60% in those without DP, and this difference was marginally significant (p=0.05). The prevalence of DP was 39%. No significant relation was found between CAR blunted and glycemic control (p>0.05).PD1 with Moderate-severe DP showed worse metabolic control than the PD1 without DP (evaluated by glycemia higher than 120 mg/dl, glycated albumin higher than 285 umol/l); p<0.05) and the relation was not significant with HbA1c but it showed a trend. Conclusions: patients with DM1 and DP presented a high prevalence of CAR blunted. DP is related with higher cardiovascular morbi-mortality, thus CAR would be useful as a biomarker of DP and would be used to stratify this population of high risk. DP moderate-severe was related to worse glycemic control, hence diagnose and treat correctly DP in PD1 would contribute to prevent the onset or the evolution of chronic complications.

Síndrome de deprivación glucocorticoidea. A propósito de un caso / Glucocorticoid deprivation syndrome. Case presentation

RESUMEN El síndrome de deprivación glucocorticoidea es el cuadro clínico resultante de la suspensión de la administración exógena de esteroides, aplicados por tiempo prolongado, independientemente de la vía de administración. Provoca la frenación del eje hipotálamo-hipófisis-suprarrenal y por ende disminuye la producción y secreción de corticotropina. Paciente femenina de 54 años de edad, con esteroides como tratamiento prolongado. Al retirarlo comenzó con pérdida de peso y dificultad para caminar, además de hipotensión ortostática, sufrió caída brusca al piso con pérdida de conocimiento. Fue llevada al hospital y no se constató pulsos periféricos ni tensión arterial, que no resolvió totalmente con el uso enérgico de fluidos endovenosos. Se mantuvo sin regular parámetros normales, se reevaluó como un síndrome de depravación corticoidea y se le impuso tratamiento con prednisona, mejorando paulatinamente. Los síndromes asociados a la retirada de corticoidesaparecen por el empleo de dosis altas, o retirada brusca de la corticoterapia prolongada. Al conjunto de síntomas y signos que aparecen cuando no se consigue tolerar la retirada de glucocorticoides, ante la ausencia de enfermedad subyacente para la cual fueron indicados estos medicamentos, y con un eje hipotálamo-hipófisis-suprarenal (HHS) no suprimido se le considera un síndrome de retirada de corticoides. A pesar de la gravedad, la frecuencia e importancia de este efecto secundario, en ocasiones no se repara en él, por lo que es imprescindible valorar los tratamientos indicados y reevaluar periódicamente los tratamientos crónicos indicados.

ABSTRACT The glucocorticoide deprivation symptom is the clinical symptom resulting from stoping the exogenous administration of steroids that were used for a long time, in spite of the administration way. It restrains the hypothalamus-pituitary-adrenal axis and therefore reduces corticotropine production and secretion. This is the case of a female patient, aged 54 years, with a continued steroid treatment. When stoping it, she began to lose weight and presented difficulties for walking. Besides orthostatic hypotension, she abruptly fell to the ground losing conciousness. She was carried to the hospital and there were not found periferal pulses nor arterial tension, a problem that was not solved by the active use of endovenous fluids. She kept on without regulating normal parameters, and was re-evaluated as a corticoid deprivation symptom and treated with prenisone. She gradually got better. The syndromes asociated to corticod deprivation begin due to the usage of high doses, or due to the abrupt withdrawal of a long corticotherapy. The whole of the symptoms appearing when corticoid withdrawal is not tolerated, in the absence of the underlying disease against which these medicines were indicated, and with a non-suppressed hypothalamus-pituitary-adrenal axis, is considered as a syndrome of corticoide withdrawal. In spite of its seriousness, of the frequency and importance of this secundary effect, sometimes it is not noticed; therefore it is essential to evaluate the indicated treatments and periodically reevaluate the treatments ordered for chronic diseases.

Study on Anti-inflammatory Effect and Its Mechanism of the Extract of Dcsmodium microphyllum / 中国药房

OBJECTIVE： To study the anti-inflammatory effect and its mechanism of the extract of Dcsmodium microphyllum， so as to provide experiment reference for further study of D. microphyllum. METHODS： Acute inflammatory model was established by xylene，glacial acetic acid and carrageenan. Using dexamethasone as positive control （0.005 g/kg）， inhibitory effects of intragastric different doses of the extract of D. microphyllum （50， 30， 15 g/kg） on xylene-induced ear swelling in normal mice and adrenalectomized mice， glacial acetic acid-induced permeability increasing of abdominal capillaries in normal mice， carrageenan-   induced paw swelling in normal mice and adrenalectomized mice were investigated. The levels of MDA， SOD and NO in the inflammatory tissue of toes of adrenalectomized mice were detected in carrageenan-induced inflammation model. Blank group was set for control （ig. equal volumn of water）. RESULTS： Compared with blank group， ear swelling degree of normal mice and adrenalectomized mice were decreased significantly in D. microphyllum extract high-dose and medium-dose groups while inhibitory rate of ear swelling was increased significantly； the permeability of abdominal capillaries of normal mice was significantly decreased in D. microphyllum extract groups； the swelling degree of toes in normal mice of D. microphyllum extract high-dose and middle-dose groups and adrenalectomized mice were significantly decreased while inhibitory rate of toe swelling was increased significantly （P＜0.05 or P＜0.01）. The levels of MDA and NO in the toe inflammatory site of adrenalectomized mice were decreased significantly in D. microphyllum extract high-dose and medium-dose groups， while the level of SOD was increased significantly （P＜0.05）. CONCLUSIONS： D. microphyllum extract can inhibit acute inflammation in mice significantly. Its anti-inflammatory mechanism is associated with decreasing MDA and NO while increasing SOD levels， and the anti-inflammatory effect does not depend on the hypothalamus-pituitary-adrenal axis system.

Effect of water extract of spina date seed and albizzia julibrissin flower on hpa axis and inflammatory cytokines in anxious depression model rats / 吉林大学学报(医学版)

Objective: To investigate the effects of spina date seed (SDS) and albizzia julibrissin flower (AJF) water extracts on the hypothalamic-pituitary-adrenal (HPA) axis and inflammatory factors IF) in the anxiety depression model rats. Methods: A total of 80 Wistar rats were randomly divided into blank group (n= 10), model group (n=10), low dose of SDS group (n=10), high dose of SDS group (n=10), low dose of AJF group (n=10), high dose of AJF group (n= 10), low dose of SDS-AJF group (n= 10), and high dose of SDS-AJF group (n=10). The rat models of anxiety depression were induced by chronic restraint stress, solitary cage and corticosterone (CORT) subcutaneous injection. The forced swimming test (FST) was used to observe the immobility time of forced swimming of the rats in various groups; Elevated plus maze test (EPM) was used to observe the open arm entry (OE), close arm entry (CE), open arm entry time (OT), and close arm entry time (CT) of the rats in various groups. The total entry of open arms and close arms (TE), OE% and OT% were calculated. ELISA method was used to detect the levels of serum corticotropin releasing hormone (CRH), adrenocorticotropic hormone (ACTH), CORT, inflammatory factors interleukin-lfi (IL-fi) and interleukin-6 (IL-6) of the rats in various groups. HE staining was used to observe the morphology of hippocampal neurons of the rats in various groups. Results: Compared with model group, the immoblity time of forced swimming of the rats in low dose of SDS-AJF group, high dose of SDS-AJF group, high dose of SDS group and high dose of AJF group was decreased (P<0. 05 or P<0. 01); compared with low dose of SDS group and low dose of AJF group, the immoblity time of forced swimming of the rats in low dose of SDS-AJF group was shortened (P<0. 05 or P< 0.01); compared with high dose of SDS group and high dose of AJF group, the immobility time of forced swimming of the rats in high dose of SDS-AJF group was shortened (P<0. 05 or P<0. 01). Compared with model group, the OE% and OT% of the rats in low dose of SDS-AJF group, high dose of SDS-AJF group, high dose of SDS group and high dose of AJF group were increased (P<0. 05 or P<0. 01); compared with low dose of SDS group and low dose of AJF group, the OE% and OT% of the rats in low dose of SDS-AJF group were increased (P<0. 05 or P<0. 01); compared with high dose of SDS group and high dose of AJF group, the OE% and OT% of the rats in high dose of SDS-AJF group were increased (P<0. 05 or P<0. 01). Compared with model group, the levels of serum CRH, ACTH, CORT, IL-1β, and IL-6 of the rats in low dose of SDS-AJF group, high dose of SDS-AJF group, high dose of SDS group and high dose of AJF group were decreased (P<0. 05 or P<0. 01); compared with low dose of SDS group and low dose of AJF group, the levels of serum CRH, ACTH, CORT, IL-1β and IL-6 of the rats in low dose of SDS-AJF group was decreased (P<0. 05 or P<0. 01); compared with high dose of SDS group and high dose of AJF group, the levels of serum CRH, ACTH, CORT, IL-1β, and IL-6 of the rats in high dose of SDS-AJF group was decreased (P<0. 05 or P<0. 01). The HE staining results showed that the hippocampal neurons of the rats in model group were loosely arranged, and a large number of nerve cells were degenerated and the cell layer was reduced. The degeneration of hippocampal neurons of the rats in low and high doses of SDS-AJF groups were significantly relieved, and the nerve cells were arranged closely and the cell layer was clear. Conclusion: Combination of SDS and AJF can improve the behavior of the rats with anxiety depression, protect the hippocampal neurons of rats, reduce the inflammatory response, and adjust the disorder of HPA axis.

Effects of Tongyuan acupuncture combined with salt and moxibustion Shenque on behavior and hypotha-lamic-pituitary-adrenal axis in postpartum depression rats / 实用医学杂志

Objective To explore the effects of Tongyuan acupuncture combined with herbal medicine and moxibustion on the behavior and hypothalamic-pituitary-adrenal axis-related hormone levels in postpartum de-pression rats.To explore the therapeutic mechanism of this method in the treatment of postpartum depression.Meth-ods A total of 120 SD rats were randomly divided into 6 groups(n=20).The blank group was not treated.The sham operation group was performed without surgery to remove the ovaries. The model group,drug group,routine acupuncture group and experimental group were established in the model of postpartum depression.After modeling successfully,the model group did not interfere with any treatment. The rats in treatment group were treated with fluoxetine hydrochloride. The acupuncture group was treated with acupuncture of Baihui and Taichong. The rats in the experimental group were treated with the method of acupuncture and moxibustion.At the end of the second and fourth week after the initiation of intervention,10 rats were randomly selected from each group.They were sacrificed and the levels of serum corticotropin-releasing hormone(CRH),adrenocorticotropic hormone(ACTH),cortisol (Cor)were measured.Results The levels of CRH,ACTH and Cor in the model group were higher than those in the blank group(P<0.05).The levels of serum CRH,ACTH and Cor in the drug group,routine acupuncture group and experimental group were lower than those in the model group(P<0.05).The levels of serum ACTH and Cor in the experimental group were lower than those in the drug group and routine acupuncture group(P<0.05).There was no significant difference in serum CRH,ACTH and Cor level between the experimental group and blank group(P >0.05).Conclusions Tongyuan acupuncture combined with salt moxibustion and Shenque have significant effects on the depressive symptoms and serum levels of CRH,ACTH and Cor in postpartum depression rats,which may be re-lated to the regulation of hypothalamic-pituitary-adrenal axis-related hormone levels.

Repetitive transcranial magnetic stimulation for treating depressive behavior in response to chronic but unpredictable mild stress / 中华物理医学与康复杂志

Objective To observe the effect of repetitive transcranial magnetic stimulation (rTMS) on behavior in response to chronic but unpredictable mild stress and explore potential neuroendocrine mechanisms.Methods Forty adult SD male rats were randomly divided into a control group (n =8) and a model preparation group (n=32).The control group was given normal care while a model of depression was induced in the model preparation group through giving an unpredictable mild stimulus (CUMS).The depressive rats were randomly divided into a model group,an rTMS group and a sham rTMS group (8 cases in each group).The rTMS group and sham rTMS groups accepted the rTMS or sham stimulation for 3 weeks.The changes in behavior in each group were quantified using body weight,sucrose consumption and an open field test before and after stimulation.Enzyme-linked immunosorbent assays (Elisas) were conducted to detect plasma adrenocorticotropic hormone (ACTH) and corticosterone (CORT) levels.Reverse-transcription polymerase chain reactions (RT-PCRs) were carried out to allow the detection of mRNA expression in hypothalamus related to levels of adrenocorticotropic hormone releasing hormone (CRH).Results After the modeling there were significant differences between the model preparation group and the control group in terms of weight increase,sucrose consumption and open field test results.After rTMS the rate of weight increase,sucrose consumption and the scores in the open field test of the rTMS group had increased significantly more than in the control group.Elisas showed significantly higher plasma ACTH and CORT levels in the model group as well.The average expression of CRH mRNA in the model group was significantly higher than in either of the other two groups.Conclusions rTMS can relieve depression-like behavior induced by chronic stress,at least in rats.This may be related to a downgrading of the hyperactive functioning of the hypothalamus-pituitary-adrenal axis.

Regulation mechanism of depression and antidepressant drug targets / 国际药学研究杂志

The etiology of depression is complex, and its incidence is related to many factors, such as social factors, genetic factors, endocrine and central nervous system functions. Antidepressant treatment effect by affecting one or more factors of the depression regulation system. This paper, based on the various hypotheses on the pathogenesis of depression proposes that the depression pathogenesis may involve central monoamine neurotransmitter systems, neural nutrients, neuro-endocrine system, nervous system and the immune system, and central nervous system tissue morphology changes, and summarizes the antidepressant drug research progress.

Improvement of kidney yang syndrome by icariin through regulating hypothalamus-pituitary-adrenal axis / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate whether Epimedium brevicornu Maxim (EB) and icariin could exert their protective effects on hydrocortisone induced (HCI) rats by regulating the hypothalamus-pituitary-adrenal (HPA) axis and endocrine system and the possible mechanism.</p><p><b>METHODS</b>Male 10-week-old Sprague Dawley (SD) rats were allotted to 6 groups (A-F) with 12 each, group A was injected normal saline (NS) 3 mL/kg day intraperitoneally, group A and B were given NS 6 mL/kg day by gastrogavage, group B-F were injected hydrocortisone 15 mg/kg intraperitoneally, group C and D were given EB 8 or 5 g/(kg day) by gastrogavage, group E and F were given icariin 25 or 50 mg/(kg day) by gastrogavage. Gene expressions of hypothalamus corticotropin releasing hormone (CRH) and pituitary proopiomelanocortin (POMC) were detected by reverse transcription-polymerase chain reaction (RT-PCR), and protein of pituitary POMC by Western-blot.</p><p><b>RESULTS</b>The serum T4, testosterone, cortisol and POMC mRNA expression were increased after treatment with EB or icariin in HCI rats, the serum CRH and the hypothalamus CRH mRNA expression released from hypothalamus corticotropin decreased compared with group B (P<0.05).The treatment with only icariin increased serum adrenocorticotropic hormone (ACTH) compared with group B (P<0.05).</p><p><b>CONCLUSION</b>EB and icariin might be therapeutically beneficial in the treatment of HCI rats through attuning the HPA axis and endocrine system which was involved in the release of CRH in hypothalamic, and the production of POMC-derived peptide ACTH in anterior pituitary, the secretion of corticosteroids in adrenal cortex.</p>

Regulation mechanism of depression and antidepressant drug targets / 国际药学研究杂志

The etiology of depression is complex, and its incidence is related to many factors, such as social factors, genetic factors, endocrine and central nervous system functions. Antidepressant treatment effect by affecting one or more factors of the depression regulation system. This paper, based on the various hypotheses on the pathogenesis of depression proposes that the depression pathogenesis may involve central monoamine neurotransmitter systems, neural nutrients, neuro-endocrine system, nervous system and the immune system, and central nervous system tissue morphology changes, and summarizes the antidepressant drug research progress.

A compared study on the executive functions and releases function of hypothalamus-pituitary-adrenal (HPA) axis in patients with single and bipolar depression disorder / 实用医学杂志

Objective To compare the executive functions and releases function of hypothalamus-pituitary-adrenal (HPA) axis in patients with single and bipolar depression disorder. Methods 32 single-phase depression (the single group) and 31 bipolar depression patients (the bipolar group) were enrolled in this study. The trail making test A and B and Stroop test (Stroop-C and Stroop-CW) were tested at 0,4 week and 8 week later. In addition,levels of 24-h urine 17-OH cortisol,24-h urine free corticosterone and plasma cortisol were also detrmined. The related results were compared among the two groups and 28 healthycontrol group. Results The TMT-A,TMT-B,Stroop-C and Stroop-CW of the baseline and at 4 week were significantly longer in the depression group than those in the control group(P<0.01,respectively), and the plasma cortisol was also higher in the depression group than that in the control (P<0.01). On baseline, the single group showed significantly longer TMT-B and Stroop-C than those in the bipolar group (P < 0.01, respectively). At 0 week, lower plasma cortisol concentrations did not appear at 12.00 AM, and the midnight deep valley secretion disappeared. However, the midnight deep valley secretion recoveried at 4 week. Conclussion The differences on executive dysfunction and excessive release of HPA-axis function between the single and the bipolar depression should be followed with interest.

Effects of early environment on emotional development and motor coordination ability of rats / 中华实用儿科临床杂志

Objeaive To explore the effects of the function of hypothalamus-pituitary-adrenal (HPA) axis on emotional development and motor coordination ability by studying the influences of early environment on long-term behaviors of developing rats.Methods Forty-five neonatal rats were randomly divided into 3 groups:the enriched environment group (EE group),the isolated environment group (IE group) and the normal environment group (NE group),with 15 cases in each group.There were 15 rats nurtured separately in EE group,IE group or NE group.The rat motor coordination abilities were tested by straight walking test on postnatal day 28 (P28) and the emotional behaviors were evaluated by handling test at P29.The levels of serum corticosterone(CORT) of rats were detected by using emission immunology method.The morphology of neural cells in rat brain was examined by adopting HE staining.Results In the straight walking test,the motor coordination abilities of rats in EE group ＞ NE group ＞ IE group(F =49.30,P ＜ 0.000).In the handing test,the scores of reaction for stressful stimuli and painful stimuli in IE group were (1.14 ± 0.36,1.93 ±0.83) ＜ (1.47 ±0.64,2.60 ±0.91) in NE group ＜ (2.07 ±0.73,3.43 ±0.65) in IE group (all P ＜ 0.01).The base serum CORT levels were (32.56 ± 9.05) μg/L in EE group ＞ (24.96 ± 6.19) μg/L in NE group ＞ (15.53 ± 6.78) μg/L in IE group (F =19.71,P ＜ 0.001).After a lower-dose adrenocorticotropic hormone stimulation test,the concentration of CORT was (18.24 ± 5.53) μg/L in EE group ＜ (21.71 ± 6.05) μg/L in NE group ＜ (28.09 ±6.51) μg/L in IE group (F=10.25,P ＜0.000).The HE staining showed the number of neural cells in striaturn and amygdale of rats were[(72.80 ±6.81) cell/HP,(73.53 ±6.14) cell/HP] in EE group ＞ [(65.67 ± 8.98) cell/HP,(61.47 ±6.57) cell/HP] in NE group ＞ [(53.33 ± 6.84) cell/HP,(48.13 ± 6.53) cell/HP] in IE group (all P ＜ 0.001).Conclusions Early environment can affect emotional reaction,motor behavior and brain development of immature rats by regulating HPA axis function.Early isolation environment can lead to HPA axis dysfunction,which can make nerve cell damage and emotion and motor coordination ability dysfunction.On the contrary,early enriched environment can moderate the hyperactivity of HPA axis after stress and promote brain development and ameliorate long-term behavioral development.

Chronic Administration of Catechin Decreases Depression and Anxiety-Like Behaviors in a Rat Model Using Chronic Corticosterone Injections

Previous studies have demonstrated that repeated administration of the exogenous stress hormone corticosterone (CORT) induces dysregulation in the hypothalamic-pituitary-adrenal (HPA) axis and results in depression and anxiety. The current study sought to verify the impact of catechin (CTN) administration on chronic CORT-induced behavioral alterations using the forced swimming test (FST) and the elevated plus maze (EPM) test. Additionally, the effects of CTN on central noradrenergic systems were examined by observing changes in neuronal tyrosine hydroxylase (TH) immunoreactivity in rat brains. Male rats received 10, 20, or 40 mg/kg CTN (i.p.) 1 h prior to a daily injection of CORT for 21 consecutive days. The activation of the HPA axis in response to the repeated CORT injections was confirmed by measuring serum levels of CORT and the expression of corticotrophin-releasing factor (CRF) in the hypothalamus. Daily CTN administration significantly decreased immobility in the FST, increased open-arm exploration in the EPM test, and significantly blocked increases of TH expression in the locus coeruleus (LC). It also significantly enhanced the total number of line crossing in the open-field test (OFT), while individual differences in locomotor activities between experimental groups were not observed in the OFT. Taken together, these findings indicate that the administration of CTN prior to high-dose exogenous CORT significantly improves helpless behaviors, possibly by modulating the central noradrenergic system in rats. Therefore, CTN may be a useful agent for the treatment or alleviation of the complex symptoms associated with depression and anxiety disorders.

Chronic Administration of Baicalein Decreases Depression-Like Behavior Induced by Repeated Restraint Stress in Rats

Baicalein (BA), a plant-derived active flavonoid present in the root of Scutellaria baicalensis, has been widely used for the treatment of stress-related neuropsychiatric disorders including depression. Previous studies have demonstrated that repeated restraint stress disrupts the activity of the hypothalamic-pituitary-adrenal (HPA) axis, resulting in depression. The behavioral and neurochemical basis of the BA effect on depression remain unclear. The present study used the forced swimming test (FST) and changes in brain neurotransmitter levels to confirm the impact of BA on repeated restraint stress-induced behavioral and neurochemical changes in rats. Male rats received 10, 20, or 40 mg/kg BA (i.p.) 30 min prior to daily exposure to repeated restraint stress (2 h/day) for 14 days. Activation of the HPA axis in response to repeated restraint stress was confirmed by measuring serum corticosterone levels and the expression of corticotrophin-releasing factor in the hypothalamus. Daily BA administration significantly decreased the duration of immobility in the FST, increased sucrose consumption, and restored the stress-related decreases in dopamine concentrations in the hippocampus to near normal levels. BA significantly inhibited the stress-induced decrease in neuronal tyrosine hydroxylase immunoreactivity in the ventral tegmental area and the expression of brain-derived neurotrophic factor (BDNF) mRNA in the hippocampus. Taken together, these findings indicate that administration of BA prior to the repeated restraint stress significantly improves helpless behaviors and depressive symptoms, possibly by preventing the decrease in dopamine and BDNF expression. Thus, BA may be a useful agent for the treatment or alleviation of the complex symptoms associated with depression.

The role of substance P to modulate the neuroendocrine function in asthmatic rats / 中国药理学通报

Aim To investigate the role of substance P in the brain of asthmatic rats.Methods Rats were injected with aluminum hydroxide and OVA allergens to prepare the animal model of asthma. Then the content of c-fos protein in asthmatic rats' brain was detected by immunohistochemical method (SABC).The content of substance P in paraventricular nucleus (PVN), the content of corticotropin-releasing hormone (CRH) in median eminence (ME), and the content of adrenocorticotropic hormone (ACTH) and corticosterone (CORT) in peripheral blood were detected by radioimmunoassay method. Then exogenous SP, SP receptor antagonist S0145 were microinjected in PVN to observe their effect upon lung function and HPA axis in asthmatic rats. Results In asthmatic rats, the content of SP increased within the PVN. The content of CRH, ACTH and CORT decreased (P<0.05).The ratio of expiratory and inspiratory and airway resistance increased. Diaphragm discharge points and lung compliance decreased (P<0.01).After microinject of SP in PVN, there was a further decrease in pulmonary function and the content of CORT, ACTH and CRH in asthmatic rats (P<0.01).While the SP receptor antagonist S0145 might reverse the change of lung function and hypothalamus-pituitary-adrenal axis (HPA axis) in asthmatic rats.Conclusion In asthmatic rats the SP in PVN can affect the function of HPA axis, involved in asthma attacks.

The suppressing effect of Shenkang 2 on HPA axis of rats model / 中国实用护理杂志

Objective To observe the inhibition effect of Shenkang 2 on rats'HPA axis,and provide theoretical basis for clinical application of steroid withdrawal and maintenance in the treatment phase.Methods To built the HPA axis suppression rat model by using high-dose glucocorticoids,when the hormone reduced to low-dose,traditional Chinese medicine Shenkang 2 were administrated.Serum ACTH,cortisol levels,adrenal index,adrenal pathological differences were observed before and after the treatment of Shenkang 2 among the treatment group,hormone control group and normal group.Results Serum ACTH,cortisol and adrenal index slowly recovered after hormone withdrawal in beth treatment group and the hormone control group,serum ACTH,cortisol and adrenal index in the treatment group rebounded faster than that in the control group,the atrophy of fascicular zone of adrenal cortex and cell disarrangement was lighter in the treatment group than that in the control group.Conclusions Shenkang 2 can improve the suppression effect of glucocorticoid-induced HPA axis suppression.

Biomarcadores de estresse em ratos exercitados por natação em intensidades igual e superior à máxima fase estável de lactato / Biomarkers of stress in rats exercised in swimming at intensities equal and superior to the maximal estable lactate phase

INTRODUÇÃO: O estresse alcançado durante exercício agudo/crônico é relevante, pois altos índices de estresse podem prejudicar o bem-estar dos animais. As concentrações dos hormônios adrenocorticotrófico (ACTH) e corticosterona, bem como as concentrações de ácido ascórbico e colesterol das glândulas adrenais são importantes biomarcadores de estresse. OBJETIVO: Analisar a sensibilidade de diferentes biomarcadores de estresse em ratos durante exercício agudo de natação em diferentes intensidades. MÉTODO: Ratos (18) adaptados à natação foram submetidos a três testes de 25 minutos suportando cargas 5,0; 5,5 e 6,0 por cento do peso corporal (PC), para obtenção da máxima fase estável de lactato (MFEL). Em seguida, os animais foram divididos em dois grupos: M (n = 9), sacrificado após 25 minutos de exercício na intensidade de MFEL e S (n = 9), sacrificado após exercício exaustivo, em intensidade 25 por cento superior a MFEL. Para comparações, um grupo controle C (n = 10) foi sacrificado em repouso. RESULTADOS: As concentrações séricas de ACTH e corticosterona foram superiores após exercício em ambas as intensidades comparadas com o grupo controle (P < 0,05). As concentrações de ACTH e corticosterona do grupo S foram, ainda, maiores do que as do grupo M (P < 0,05). As concentrações de colesterol e ácido ascórbico na adrenal dos grupos exercitados (M e S) foram inferiores às do grupo controle (P < 0,05). Não houve diferença das concentrações de ácido ascórbico e colesterol da adrenal quando comparadas as duas intensidades de exercício (M e S) (P < 0,05). CONCLUSÃO: Todos os biomarcadores do eixo HHA apontaram alterações no nível de estresse de ratos submetidos a exercício agudo de natação; as concentrações séricas de ACTH e corticosterona mostraram-se mais sensíveis a pequenas alterações na intensidade do exercício.

INTRODUCTION: The level of stress during acute/chronic exercise is important, since higher levels of stress may impair animal welfare. The adrenocorticotrophic (ACTH) and corticosterone hormone concentrations, as well as cholesterol and ascorbic acid concentrations in adrenal gland, are considered an important stress biomarker. PURPOSE: To analyze the sensitivity of the different biomarkers during acute swimming exercise in different intensities performed by rats. METHODS: Male Wistar adult rats (n = 18) previously adapted to swimming were submitted to three 25 min. swimming tests with loads of 5.0; 5.5 and 6.0 percent of their body weight (BW), for maximum lactate steady state (MLSS) determination. After MLSS attainment, the animals were divided into two groups: M (n = 9) sacrificed shortly after a 25 min. session of exercise at the MLSS intensity or S (n = 9) sacrificed after exhaustive exercise at intensity 25 percent above MLSS. For comparison purposes, a control group C (n = 10) was sacrificed in rest. RESULTS: Serum ACTH and corticosterone concentrations were higher after exercise for the two groups (M and S) when compared with control group C (P < 0.05). The group S presented higher concentrations for both hormones in relation to the group M (P < 0.05). The concentrations of the cholesterol and ascorbic acid in adrenal were lower after exercise for the two groups (M and S) when compared with control group C (P < 0.05). No significant differences in adrenal ascorbic acid and cholesterol levels were observed when the two exercise intensities (M and S) were compared (P < 0.05). CONCLUSION: All biomarkers of HPA activity pointed alterations in the stress level of the rats submitted to acute swimming exercise. ACTH and corticosterone serum concentrations showed to be more sensitive to small alterations in the effort intensity.