OBJECTIVES: To explore the damage effects of chronic restraint stress (CRS) on amygdala cells through the rat CRS model. METHODS: The rat CRS model was established, and the changes in body weight and adrenal mass in control group and CRS group were monitored at 1 d, 7 d, 14 d and 21 d. The behavior changes were evaluated by the percentage of retention time of open arms and open arm entries using the elevated plus maze (EPM). ELISA was used to detect the concentrations of rat's corticotropin releasing hormone (CRH), adrenocorticotropic hormone (ACTH) and cortisol. The changes of expression of glucocorticoid receptor (GR) and glial fibrillary acidic protein (GFAP) in amygdala were determined by immunohistochemistry and Western blotting. Ultrastructure changes of glial cell were observed by transmission electron microscopy. The apoptosis rate of amygdala was measured by flow cytometry. RESULTS: Compared with the control group at the same time points, body weight of CRS 1 d, 7 d, 14 d and 21 d groups increased slowly, but adrenal mass increased significantly; the serum level of CRH, cortisol and ACTH increased significantly at 7 d, 14 d and 21 d respectively; the expression of GR in amygdala was increased while that of GFAP was decreased; EPM test suggested that the percentage of retention time of open arms and open arm entries decreased significantly after 14 d. The CRS group showed different degrees of glial cell damage in amygdala, and the apoptosis rate of glial cell was significantly increased in 21 d group. CONCLUSIONS This study successfully established a CRS model in rats, and anxiety-like behavioral changes in model rats may be caused by apoptosis of amygdala astrocytes.
Rats ; Animals ; Hydrocortisone/pharmacology* ; Amygdala/metabolism* ; Adrenocorticotropic Hormone/pharmacology* ; Apoptosis ; Body Weight

Because high levels of cortisol are frequently observed in patients with septic shock, low levels of serum cortisol are considered indicative of relative adrenal insufficiency (RAI). This study was performed to investigate whether pretest clinical characteristics, including basal serum cortisol levels, are predictive of serum cortisol response to corticotropin and whether basal cortisol levels have a prognostic significance in patients with septic shock. We performed a retrospective analysis of 68 patients with septic shock who underwent short corticotropin stimulation testing. RAI was defined as an increase in cortisol level <9 microgram/dL from baseline, and results showed that 48 patients (70.6%) had this insufficiency. According to the univariate analysis, the RAI group had significantly higher simplified acute physiology score II (SAPS II) and sequential organ failure assessment (SOFA) scores than the non-RAI group. The incidence of RAI was the same regardless of the basal serum cortisol level (p=0.447). The hospital mortality rate was 58.8% and was not significantly different between the RAI and non-RAI groups. However, a high basal serum cortisol level (> or =30 microgram/dL) was significantly associated with in-hospital mortality. In conclusion, our data suggest that basal serum cortisol levels are not predictive of serum cortisol response to corticotropin but have a significant prognostic value in patients with septic shock.
Adrenal Insufficiency/blood/diagnosis ; Adrenocorticotropic Hormone/*pharmacology ; Aged ; Female ; Humans ; Hydrocortisone/*blood ; Incidence ; Male ; Middle Aged ; Prognosis ; Reference Values ; Shock, Septic/*blood/*diagnosis/mortality ; Time Factors ; Treatment Outcome

OBJECTIVETo observe the effects of acute immobilization stress on the mRNA expression of tyrosine kinase B (TrkB) in rats' hippocampus.

METHODSEighteen SD rats were randomly divided into three groups, i.e., the normal control group, the model group, and the medication group, 6 in each group. The acute immobilization stress model was prepared in the model group using acute immobilization for 2 h. Ginsenoside Rb1 (40 mg/kg) was peritoneally injected to rats in the medication group 30 min before modeling, with the same procedure as those for rats in the model group. No treatment was performed to rats in the normal control group. The plasma adrenocorticotropic hormone (ACTH) and corticosterone (CORT) contents were detected using ELISA. The mRNA expression of TrkB in the rats' hippocampus was detected using real-time fluorescence quantitative RT-PCR.

RESULTSBefore modeling there was no statistical difference of plasma CORT or ACTH concentrations among three groups (P >0.05). The plasma CORT and ACTH concentrations increased in the model group and the medication group more significantly after modeling than before modeling, showing statistical difference (P <0.05). Besides, they were obviously higher in the model group than in the normal control group (P <0.05). They were obviously higher in the medication group than in the model control group (P <0.05). Compared with the normal control group, the mRNA expression of TrkB significantly decreased in the model group (87.73 +/- 7.62 vs 50.65 +/- 5.19, P < 0.05), showing statistical difference. The mRNA expression of TrkB was significantly higher in the medication group (78.91 +/- 18.07) than in the model group, showing statistical difference (P <0.05).

CONCLUSIONPretreatment by ginsenoside Rb1 could increase the plasma CORT and ACTH concentrations, maintain the mRNA expression of TrkB, thus relieving injury induced by acute immobilization stress.

Adrenocorticotropic Hormone ; blood ; Animals ; Corticosterone ; blood ; Ginsenosides ; pharmacology ; Hippocampus ; metabolism ; Male ; RNA, Messenger ; genetics ; Rats ; Rats, Sprague-Dawley ; Receptor, trkB ; genetics ; metabolism ; Stress, Psychological ; metabolism

Ginseng is a typical adaptogen which has resistance to various stresses. This effect is related to the hypothalamic-pituitary-adrenal (HPA) axis. As the main active ingredients, saponin has the similar structure to steroids. The regulation characteristics of ginseng saponin on the HPA axis are narrated from the aspects of total saponin and saponin monomers in this paper after the introduction of adaptation definition and HPA axis regulation mechanisms. Pharmacological effects of ginseng saponin and the regulation effect of HPA axis are summarized finally.
Adaptation, Physiological ; Adrenocorticotropic Hormone ; secretion ; Animals ; Corticosterone ; secretion ; Ginsenosides ; isolation & purification ; pharmacology ; Humans ; Hypothalamo-Hypophyseal System ; drug effects ; secretion ; Panax ; chemistry ; Pituitary-Adrenal System ; drug effects ; secretion

AIMTo study the regulation effects of Momordica saponins on endocrine function in senile mice.

METHODS15-month Kunming mice (female), were divided into senile control group (SC), experimental group 1 and 2 (E1 and E2). 10 4-month mice were as young control group (YC). All mice were fed with general foodstuff, SC and YC drank tap water, while two experimental groups drank tap water supplied to 100 mg/L and 200 mg/L Momordica saponins respectively. Serum was assayed after 5 weeks. At the same time, levels of estrogen receptor and its mRNA were assayed in cultured thymocyte from 12-month rat.

RESULTSSerum ACTH and estradiol levels declined markedly in senile mice compared with young mice. ACTH levels increased in some extent in two experimental groups, while there had significant difference only in E2. Serum estradiol increased obviously, but there was no significant distinct between E1 and E2. The most important was that ER levels increased obviously, and there was no any change of ER mRNA levels in rat thymocyte cultured in medium contained different content of Momordica saponins.

CONCLUSIONMomordica saponins could improve endocrine function in senile mice by increasing ACTH level and expression of ER.

Adrenocorticotropic Hormone ; metabolism ; Aging ; drug effects ; Animals ; Female ; Mice ; Mice, Inbred Strains ; Momordica ; chemistry ; Receptors, Estrogen ; metabolism ; Saponins ; pharmacology ; Thymocytes ; drug effects ; metabolism

OBJECTIVETo compare changes of hypothalamus-pituitary-adrenal axis (HPAA) in different rat models of Gan stagnation (GS), Pi deficiency (PD), Gan stagnation Pi deficiency (GSPD) syndromes, and to observe interventional effect of Chaishu Sijun Decoction (CSD, capable of soothing Gan-qi invigorating Pi) on them.

METHODSSeventy Wistar rats were divided into the normal control group (group 1), the GS group (group 2), the PD group (group 3), the GSPD group (group 4), the GS intervention group (group 5), the PD intervention group (group 6), and the GSPD intervention group (group 7) according to random digit table, 10 in each group. Rats in group 1 received no treatment. Rats in group 2 and 5 were modeled by chronic restraint method. Rats in group 3 and 6 were modeled by excess fatigue plus alimentary abstinence method. Rats in group 4 and 7 were modeled by chronic restraint, excess fatigue, and alimentary abstinence method. At the 2nd weekend of modeling, CSD at 2.86 g/kg was fed to rats in group 5, 6, and 7 by gastrogavage for 2 successive weeks. Equal volume of distilled water was given to rats in the rest 4 groups. On the 29th day, rats were killed, adrenal weight weighed, and adrenal index calculated. Levels of plasma and hypothalamus corticotropin-releasing hormone (CRH), plasma and pituitary adrenocorticotrophic hormone (ACTH), and plasma corticosterone (CORT) were determined using radioimmunity.

RESULTSCompared with group 1, adrenal index significantly decreased in group 2, 3, and 4 (P < 0.05). Of them, plasma and hypothalamus CRH, plasma CORT increased significantly in group 2 and 4 (P < 0.05). Besides, plasma and pituitary ACTH increased in group 4 (P < 0.05). Plasma and pituitary ACTH, as well as plasma CORT decreased significantly in group 3 (P < 0.05). Compared with group 2, 3, and 4, adrenal index increased significantly in group 5, 6, and 7 (P < 0.05). Compared with group 2, plasma CORT, hypothalamus CRH, and pituitary ACTH decreased significantly in group 5 (P < 0.05). Compared with group 3, plasma ACTH and CORT increased significantly in group 6 (P < 0.05). Compared with group 4, plasma CRH, ACTH, CORT, hypothalamus CRH, and pituitary ACTH decreased in group 7 (P < 0.05).

CONCLUSIONSThe function of HPA .axis was damaged to varying degrees in rats of the three models in this experiment. Hyperactivity of HPA axis existed in GS syndrome and GSPD syndrome. Impairment of feedback regulation in hypothalamus and pituitary was accompanied in GSPD syndrome. Hypofunction of HPA axis existed in PDS. CSD, capable of soothing Gan-qi invigorating'Pi, showed improvement on disarranged HPAA, but with optimal effect on GSPD syndrome. CSD had higher correlation with GSPD syndrome.

Adrenocorticotropic Hormone ; metabolism ; Animals ; Corticosterone ; Corticotropin-Releasing Hormone ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Hypothalamo-Hypophyseal System ; metabolism ; Hypothalamus ; metabolism ; Medicine, Chinese Traditional ; Models, Animal ; Pituitary Gland ; metabolism ; Pituitary-Adrenal System ; metabolism ; Rats ; Rats, Wistar

OBJECTIVE: To observe the effects of triptolide on the hypothalamic-pituitary-adrenal axis (HPAA) of rats in light of morphological and functional changes. METHODS: Thirty Sprague-Dawley (SD) male rats were randomized into 3 groups and given 2% propylene glycol, mixture of propylene glycol and prednisone acetate or compounds of propylene glycol and triptolide by gavage, respectively, for consecutive 7 weeks. Determination in the 3 groups was conducted concerning the contents of blood plasma cortisol (COR), adrenocorticotropic hormone (ACTH) and corticotropin-releasing hormone (CRH) besides measurement of the rats' body weight, coefficient of the adrenal gland and observation of the histopathological changes in fascicular zone of adrenal cortex. Immunohistochemical staining technique was used to detect the expression of ACTH in pituitary in the 3 groups. RESULTS: (1) The content of COR in the groups of triptolide and prednisone acetate appeared lower and serum ACTH showed no significant difference, but CRH in the group of triptolide was augmented as compared with the control group (P < 0.05). (2) The rats' weight in the groups of triptolide and prednisone acetate was declined, and yet, the coefficient of the adrenal gland remained no significant change in comparison with the controls. HE staining and electron microscopy examination revealed thinned and constricted zona fasciculata in adrenal gland in the rats of triptolide and prednisone acetate, with hypofunction. ACTH expression in the group of triptolide was higher than that of the control group (P < 0.05). CONCLUSION Morphologically and functionally, the findings suggest that long-term use of triptolide may result in atrophied cortex and hypofunction of the adrenal gland, leading to augmented production and secretion of CRH and ACTH from respective hypothalamic and pituitary.
Adrenal Cortex/physiopathology* ; Adrenocorticotropic Hormone/metabolism* ; Animals ; Corticotropin-Releasing Hormone/metabolism* ; Diterpenes/pharmacology* ; Epoxy Compounds/pharmacology* ; Hydrocortisone/blood* ; Hypothalamo-Hypophyseal System/physiopathology* ; Immunohistochemistry ; Male ; Phenanthrenes/pharmacology* ; Pituitary-Adrenal System/physiopathology* ; Prednisone/pharmacology* ; Propylene Glycol/pharmacology* ; Random Allocation ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo explore the effect of Changji'an Capsule (CA) on mRNA expressions of neuropeptide Y (NPY) in the hypothalamus and colon and serum levels of adreno-cortico-tropic hormone (ACTH) in rats of diarrhea predominant irritable bowel syndrome (IBS-D) model rats.

METHODSTotally 48 SD rats were randomly divided into six groups, i.e., the normal control group, the model group, the Pinaverium Bromide group (PB, 0.018 g/kg), the high dose CA group (2.812 g/kg), the medium dose CA group (1.406 g/kg), and the low dose CA group (0.703 g/kg), 8 in each group. The IBS-D rat model was established by using separation of breast milk + stimulation of acetic acid + constraint of four limbs. Normal saline was given to rats in the normal control group and the model group. All medication lasted for 14 successive days by gastrogavage. The serum content of ACTH was detected by enzyme linked immunosorbent assay (ELISA). The expressions of NPY mRNA in the colon and the hypothalamus were detected using real-time fluorescence quantitative PCR.

RESULTSCompared with the normal control group, the serum ACTH content significantly increased (P < 0.01), the NPY mRNA expression in the colon and the hypothalamus obviously decreased (P < 0.01) in the model control group. Compared with the model group, the serum ACTH obviously decreased in the high dose CA group, the medium dose CA group, and the PB group (P < 0.01, P < 0.05). The NPY mRNA expression in the colon and the hypothalamus were obviously up-regulated in the high dose CA group, the medium dose CA group, the low dose CA group, and the PB group (P < 0.05).

CONCLUSIONSCA could modulate the abnormity of brain-gut axis of IBS-D rats possibly by up-regulating NPY mRNA expressions in the hypothalamus and the colon and down-regulating the ACTH content in the hypothalamic-pituitary-adrenal axis.

Adrenocorticotropic Hormone ; blood ; Animals ; Colon ; metabolism ; Disease Models, Animal ; Drugs, Chinese Herbal ; pharmacology ; Female ; Hypothalamus ; metabolism ; Irritable Bowel Syndrome ; metabolism ; Male ; Neuropeptide Y ; metabolism ; RNA, Messenger ; genetics ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo explore the effect of Jingui Shenqi pill (JGSQP) with various concentrations at different time points on pituitary adrencorticotropic hormone (ACTH) gene expression level in Shen-Yang deficiency rats.

METHODSThe Shen-Yang deficiency rats were randomly divided into the model control group and the high, medium and low dosage of JGSQP groups. Reverse transcriptase polymerase chain reaction was used to observe the effect of JGSQP on the ACTH mRNA of pituitary tissue in rats treated at different time points (10 d, 20 d, 30 d).

RESULTSAs compared with that in the model group, the ACTH gene expression level was significantly higher in the high dose JGSQP group (P < 0.05), and the increment in the medium dosage group was significantly higher in comparing with that in the high and low dosage groups (P < 0.05 or P < 0.01).

CONCLUSIONThrough up-regulation on ACTH gene expression is possibly one of the mechanisms of JGSQP in treating Shen-Yang deficiency.

Adrenocorticotropic Hormone ; biosynthesis ; genetics ; Animals ; Drugs, Chinese Herbal ; pharmacology ; Hypothalamo-Hypophyseal System ; Kidney Diseases ; genetics ; metabolism ; Medicine, Chinese Traditional ; Pituitary Gland ; metabolism ; RNA, Messenger ; biosynthesis ; genetics ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Yang Deficiency ; genetics ; metabolism

OBJECTIVETo study the effect of Jiaweisinisan (JWSNS), a traditional Chinese herbal medicinal recipe, on gastric mucosal ultrastructure and brain-gut axis in rat models of chronic psychological stress and elucidate the mechanism of JWSNS for ameliorating stress-induced gastrointestinal dysfunction.

METHODSSixty rats were randomly assigned into normal control group, model group, 3 JWSNS groups (high, moderate, and small doses), and omeprazole group (n=10). Rat models of chronic psychological stress were established by random stressful stimulations, and following the corresponding interventions, plasma adrenocorticotropic hormone (ACTH) and cortisol (CORT) levels were detected using radioimmunoassay, and the mRNA expressions of gastrin receptor in the gastric tissue (GASR) and vasoactive intestinal peptide II receptor (VIPR2) in the jejunal tissue were examined using RT-PCR. Transmission electron microscopy was employed to examine the ultrastructural changes in the gastric mucosa tissue cells of the glandular stomach area and alterations in the intercellular junctions.

RESULTSElectron microscopy revealed obvious damages in gastric mucosal epithelial cell organelles and nuclei in the model rats. These damages were ameliorated after treatments with JWSNS and omeprazole. Compared with the model group, the 3 JWSNS groups and omeprazole group all showed significantly lowered plasma ACTH and CORT levels, increased gastrin receptor mRNA expression and decreased jejunal VIPR2 mRNA expression (P<0.05 or 0.01).

CONCLUSIONJWSNS can obviously ameliorate the pathologies of the gastric mucosa cells, regulate the state of brain-gut axis, and modulate the gastric gastrin receptor and jejunal VIPR2 mRNA expressions in rats with chronic psychological stress.

Adrenal Cortex Hormones ; blood ; Adrenocorticotropic Hormone ; blood ; Animals ; Drugs, Chinese Herbal ; pharmacology ; Gastric Mucosa ; metabolism ; pathology ; ultrastructure ; Hydrocortisone ; blood ; Jejunum ; metabolism ; Male ; Rats ; Rats, Wistar ; Receptors, Bombesin ; metabolism ; Receptors, Vasoactive Intestinal Peptide, Type II ; metabolism ; Stress, Psychological ; pathology