Effects of repetitive transcranial magnetic stimulation on hypothalamic-pituitary-adrenal axis of patients with depression

Objective: To investigate the effects of sleep electroencephalogram-modulated repetitive transcranial magnetic stimulation (SEM-rTMS) and conventional rTMS (C-rTMS) on the activity of hypothalamic-pituitary-adrenal (HPA) axis in patients with depression. Methods: In a double-blind, randomized controlled trial, 164 patients diagnosed with depression were randomized to treatment with SEM-rTMS (n=57), C-rTMS (n=55) or sham rTMS (n=52) for 30 min every day for 10 d. Before and after treatment plasma concentrations of adrenocorticotropic hormone (ACTH) and cortisol (CORT) were measured, and the 24-item Hamilton Depression Rating Scale (HAMD-24) was used for assessment. Results: The HAMD-24 scores and plasma ACTH and CORT concentrations of these depressive patients before treatment were significantly different from those of the normal control group (P<0.05). The HAMD-24 scores and plasma ACTH and CORT concentrations in the SEM-r TMS group and conventional rTMS group were decreased significantly (P<0.05). There was a significant positive correlation between the HAMD-24 scores and plasma ACTH (n=240, r=0.105, P=0.048) and CORT concentrations (n=240, r=0.126, P=0.023) in the patients with depression before and after treatment. Conclusion: The antidepressant effect of rTMS, including SEM-rTMS, may be related to its decreasing HPA axis activity. (This trail was registered. No: ChiCTR-TRC-00000465)

Electroacupuncture (EA) Speeds Up the Regulation of Hypothalamic Pituitary Adrenal Axis Dysfunction in Acute Surgical Trauma Rats: Mediated by Hypothalamic Gamma-Aminobutyric Acid (GABA)_AReceptors

Hypothalamic Corticotropin-releasing factor (CRF) directly activates the hypothalamic pituitary adrenal axis (HPA axis) during the surgical trauma induced stress response. Electroacupuncture (EA) has been demonstrated to have stress relieving effects in breast surgery, colorectal surgery, prostatectomy and craniotomy. This study was aimed to investigate the hypothesis that EA could regulate hypothalamic CRF in surgical trauma rats. In experiment one, Sprague-Dawley (SD) male rats were divided into intact, model (10% partial hepatectomy), sham EA and EA group. Rats from the Sham EA and EA group were stimulated at ST36-Zusanli and SP6-Sanyiniiao acupoints twice, 24 hours before the surgery and immediately after the surgery. Expressions of hypothalamic CRF and CRFR, GABA receptors, glutamate decarboxylase (GAD), serum adrenocorticotropic hormone (ACTH) and Corticosterone (CORT) were observed at 2, 4, 8 and 24 h after the surgery by radioimmunoassay (RIA), western blot, real-time PCR and immunohistochemistry. In the experiment two, SD male rats were divided into the intact, model, model + vehicle, model + L-838,417 EA and EA + L838,417 group. It was found that hypothalamus CRF, serum ACTH and CORT levels were increased in model group compared with the intact group, and those in the EA group decreased in comparison with the model group. Compared with the model group, hypothalamus-aminobutyric acid (GABA) receptor Aα3 mRNA and protein expressions of the EA group raised strikingly. In conclusion, EA alleviated surgical stress response by improving the GABA synthesis in hypothalamus, thus enhancing GABA receptors’ inhibitory regulation of the HPA axis dysfunction in rats with acute surgical trauma.

The total flavonoids extracted from Xiaobuxin Tang reverse the hyperactivity of hypothalamic-pituitary-adrenal axis in chronically stressed rats

Objective To investigate the effect of XBXT-2 on the activity of hypothalamic-pituitary-adrenal(HPA)axis in chronic mild stress(CMS)model of rats.Methods Using ELISA to test the serum corticosterone,adrenocorticotropic hormone(ACTH)and corticotropin-releasing hormone(CRH)level in CMS rats;Using western blot to determine hippocampal glucocorticoids receptors(GR)expression in CMS rats.Results Co-administration of XBXT-2(25,50 mg·kg-1,p.o.,28 days,the effective doses for behavioral responses)significantly decreased the serum corticosterone and ACTH level in CMS rats,while the CRH level was not markedly affected by chronic stress or drugs.Moreover,XBXT-2 significantly increased the GR expression in the hippocampus of CMS rats.The same effects were observed in the positive control drug imipramine(10 mg·kg-1,p.o.).Conclusions The decrease of serum corticosterone and ACTH level,as well as the increase of hippocampal GR expression may be the mechanisms underlying the antidepressant action of XBXT-2,which may associate with HPA axis.

Individual Differences in Stress Responsiveness of the Hypothalamic-Pituitary-Adrenal Axis and Its Vasopressinergic Regulation in Old Monkeys

Stress adaptation is fundamental for health, and the hypothalamic-pituitary-adrenal axis (HPA) is one of its main mechanisms. Considerable data indicate that arginine vasopressin (AVP) related disturbances of stress adaptation can occur with aging. However, most studies of such kind have been performed on rodents, give contradictory results and fail to consider individual characteristics of the animals. The purpose of this study was to investigate individual HPA responsiveness to acute stress and its vasopressinergic regulation in old female rhesus monkeys that differ in their behavioral responses to stress. Animals with depression-like or anxiety-like behavior (DAB) responded with higher plasma levels of ACTH and AVP, lower levels of corticosteroids and higher cortisol/DHEAS molar ratios to restraint stress and to insulin-induced hypoglycemia compared with animals with healthy adaptive behavior. AVP and ACTH dynamics were closely correlated in most animals. AVP treatment produced differences in HPA responses similar to those produced by the stressors. The ACTH response to hypoglycemic stress in the DAB animal with highest HPA responsiveness was dramatically reduced by prior administration of a V1b receptor antagonist. These results suggest that the dysfunctions of HPA observed in old animals with DAB are caused by increased tone of the vasopressinergic system in regulation of HPA stress reactivity.

Anti-anxiety effect of Valeriana jatamansi Jones extract via regulation of the hypothalamus-pituitary-adrenal axis

BACKGROUND： Hypothalamus-pituitary-adrenal （HPA） axis dysfunction has been closely linked to anxiety. Previous studies have shown that Valeriana jatamansi Jones extract exhibits clear anxiolytic effects, but it is unclear about the mechanism underlying regulation of the HPA axis dysfunction in these anxiolytic effects. OBJECTIVE： To observe the effects of Valeriana jatamansi Jones （Zhizhu Xiang） extract on HPA axis function in a rat model of anxiety, and to compare these effects with positive control estazolam. DESIGN, TIME AND SETTING： Randomized, controlled, animal experiment was performed at Chengdu University of Traditional Chinese Medicine, China, between February and September in 2006. MATERIALS： Estazolam was purchased from Shanghai Jiufu Pharmaceutical, China; Valeriana jatamansiJones was purchased from the Lotus Pond Market for Chinese Herbal Medicine in Chengdu. It consisted of iridoids and flavonoid components. METHODS： A total of 72 Sprague Dawley rats, aged 2 months, were randomly assigned to 6 groups low-, medium-, and high-dose Valerianajatamansi Jones groups intragastrically injected with 0.3, 0.6, and 0.9 g/kg per day Valerianajatamansi Jones extract, respectively; estazolam group intragastrically injected with 1.5 mg/kg per day estazolam; model and normal groups administered 5 mL physiological saline. Anxiety was established in all groups, except the normal group, through the use of elevated plus-maze test at 7 days following drug administration. MAIN OUTCOME MEASURES： Blood β-endorphin and corticosterone levels were determined using enzyme-linked immunosorbent assay following treatment with ValerianajatamansiJones extract. Expressions of HPA axis-related genes were measured by cDNA microarray. RESULTS： Blood β-endorphin and corticosterone levels were significantly greater in the model group than in the normal group. Compared with the model group, levels decreased with Valeriana jatamansi Jones extract or estazolam treatment, particularly in the low-dose Valeriana jatamansi Jones group （P〈 0.01）. cDNA microarray results demonstrated that corticotropin-releasing hormone and Orexin, which are associated with HPA axis function, were differentially expressed; expression increased in the model group, but decreased in rats treated with Valerianajatamansi Jones extract. CONCLUSION： Valerianajatamansi Jones extract plays a role in regulating HPA axis function in a rat model of anxiety, and this effect was superior to estazolam.

Relationship between glutamate in limbic system and hypothalamuspituitary-adrenal axis after middle cerebral artery occlusion in rats

Objective To study the features of the activity changes of glutamate (GLu ) in the hippocampusand hypothalamus and its effects on the activation of the hypothalamus-pituitary-adrenal axis (HPA ) duringacute cerebral ischemia (ACI ). Methods: The changes of Glu content, corticotrophin releasing hormone(CRH ) mRNA expression level and adrenocorticotropic hormone (ACTH ) concentration were determinedwith high-performance liquid chromatography (HPLC ) and in situ hybridization in different time intervals after middle cerebral artery occlusion (MCAO) in rats. Results: Glu content was increased rapidly in the hippocampus and hypothalamus 15 min after MCAO and reached the peak (the average Glu content in the hippocarnpus and hypothalamus were 21. 50± 2. 88 mg/g wt and 14. 20±2. 58 mg/g wt respectively) in the lsthour after MCAO and it returned rapidly to the base line level after reperfusion. The Gln content in the hippocampus and hypothalamus went up once more in the 24th hour of reperfusion, remained at a relatively highlevel till the 48th hour of reperfusion and then declined gradually. The expression level of CRH mRNA wasmarkedly enhanced in the temporal cortex, hippocampus and hypothalamus in the lst hour after MCAO andthis condition was kept on till the 96th hour of reperfusion. In the same time, the plasma level of ACTH wasrelatively increased. In the peak stage of reperfusion injury,there was a positive correlation of the Glu contentin the hypothalamus with the number of positive cells of CRH mRNA expression and the plasma level of ACTH. Conclusion: The central CRH system is possible to locate mainly in the limbic system and Gln might beone of the factors to induce excessive excitable stress response of the HPA axis.

Prolonged Adrenal Insufficiency after Unilateral Adrenalectomy for Cortisolic Adenoma

Background: The suppression of the hypothalamic-pituitary-adrenal axis by cortisol-secreting adrenocortical tumors is well recognized and requires peri- and postoperative hydrocortisone substitution. Case Presentation: A 48-year-old female patient with hypertension and progressive weight gain, the clinical signs of hypercorticism motivated a hormonal workup revealing an independent ACTH Cushing’s syndrome: with urinary free cortisol (UFC) at 649 nmol/24h (4× normal), adrenocorticotropin hormone (ACTH) at 1.5 ng/l. The rest of the hormonal workup was not performed due to a lack of financial means. An Adrenal CT scan showed a 4 cm right adrenal adenoma. The patient underwent a right adrenalectomy with an adrenal adenoma on pathological examination. The contralateral side was normal. The patient was treated with hydrocortisone 30 mg/d for 6 weeks then 15 mg/d, during the monitoring we noted a persistence of the adrenal insufficiency for now 4 years. Basal cortisol levels during follow-up were very low (<3 μg/dl) ruling out the need for synacthen stimulation tests. Conclusion: Adrenal cortisol tumors are recognized by suppression, the duration of hypothalamic-pituitary-adrenal axis suppression is variable from 11 to 60 months depending on the series, which depends on the duration, severity of hypercortisolism, tumor size and other unknown factors. A longer follow-up of these patients is necessary to look for recovery of the contralateral adrenal gland.

Heshouwu decoction, a Chinese herb for tonifying kidney, ameliorates hypothalamic-pituitary-testicular axis secretion in aging rats

An increasing amount of evidence demonstrates the anti-aging effect of Heshouwu in pill form. In this study, a subacute aging rat model was established by continuous intraperitoneal injection of D-galactose and treated with Heshouwu decoction （a Chinese herb for tonifying the kidney, comprising Heshouwu pill, Herba Epimedii, Radix Salviae Miltiorrhiae, and Poria）. Heshouwu pill treated rats were the positive control group. Radioimmunoassay, immunohistochemical staining, and western blot assay showed hypothalamic gonadotropin-releasing hormone, hypothalamic substance P, and serum gonadotropin levels to be significantly increased in the model rats; the concentrations of hypothalamic ~3-endorphin, and serum levels of insulin-like growth factor I and testosterone were significantly decreased. 1713- and 3[3-hydroxysteroid dehydrogenase expression in testicular tissue was also decreased. Intragastric administration of Heshouwu decoction at high （9.6 g/mL/100 g）, medium （4.8 g/mL/100 g）, and low （2.4 g/mlJ100 g） doses, Heshouwu decoction pretreatment at a medium dose （4.8 g/mL/100 g）, and Heshouwu pill （2.06 g/mL/100 g） significantly reversed these changes. Heshouwu decoction pretreatment and high-dose Heshouwu decoction had the greatest anti-aging effects. These experimental findings indicate that Heshouwu decoction can improve hypothalamic-pituitary-testicular axis secretion in a subacute aging rat model, and prevent and delay gonadal axis aging, with an effect superior to that of Heshouwu pill.

Interaction between Neuroendocrinology and Immunology: Hypothalamic-Pituitary-Thyroid Axis in Immunoendocrinology

The study of interactions between neuroendocrinology and immunology, or immunoendocrinology, is a recent field with the majority of its development in the last 30 years that involves communication between the nervous, endocrine, and immune systems. Homeostasis, development, aging, metabolism, infection, and inflammation are all influenced by the cross talk between these systems via hormones, cytokines, and neurotransmitters. The nervous system affects the immune system through either the hypothalamus-pituitary axes (adrenal, gonadal, thyroid, growth-hormone) neuropeptide and hormone signals or autonomic nervous system signals of norepinephrine and acetylcholine. On the other hand, the immune system passes feedback through cytokine type and concentration in the blood. Imbalance of any of these systems leads to increased risk in severity of metabolic, psychiatric, inflammatory or autoimmune diseases. These two systems are complex standalone and even more so in their interaction. Thus, the relationship between the immune system and the hypothalamus-pituitary-thyroid axis is necessary to be reviewed.

Effects of BPA and E2 on expression profiles of genes related to hypothalamic-pituitary-gonadal axis of half-smooth tongue sole Cynoglossus semilaevis

Endocrine disrupting chemicals (EDCs) are increasingly viewed as persistent pollutants, similar to natural hormones in function. This paper describes the expression profiles of 7 genes (DMRT, VTG, GnRHR, FSHR, CYP17A, CYP19A, and CYP19B) involved in sex steroid synthesis and action as well as sexual development in adult male and female Cynoglossus semilaevis, after exposure to different concentrations of Bisphenol A (BPA) and 17β-estradiol (E2). Both BPA (1, 10, 50, 125, and 250 mg/kg) and E2 (0.5, 5, and 10 mg/kg) induced changes in target gene expression, although the estrogenic effects of E2 as a model estrogen were stronger. Among the 7 genes, VTG, CYP17A and CYP19 responded strongly to BPA or E2 exposure and can thus serve as reference biomarkers for estrogenic EDCs exposure in marine teleosts. These data will provide a window to establish a hypothalamic-pituitary-gonadal model in C. semilaevis to better understand the effect pathways of EDCs.

Clinical Significance of Multiple Hypothalamic－Pituitary Functions Assessment in Patients with Turner＇s Syndrome

Hypothalamic-pituitary functions in 26 cases of Turner syndrome were assessed with a combined stimulation test.The results showed that the peak GH levels of 12 cases were less than 10 μg/L; 3 patients were demonstrated as having an even TSH response, while another one with a delayed TSH peak, and other 4 had high basal values and consistent exaggerated TSH responses to TRH; all patients showed increased basal and peak LH and FSH levels but 5, whose LH and FSH secretion patterns were similar to normal. 12 cases have been treated with individualized protocols and followed up for 12 months or more, of them the growth velocity all increased, especially those with hypothyroidism or with a BA less than 13. It is suggested that multiple functions of hypothalamic-pituitary axis in Turner patients be evaluated as early as possible, in order that proper treatment could be adopted and their growth and development improved.

MAGNETIC RESONANCE IMAGES OF THE HYPOTHALAMIC-PITUITARY AREA IN IDIOPATHIC GROWTH DEFICIENCY

In order to describe the magnetic resonance imaging (MRI) findings in hypothaiamic-pituitary area and its clinical relevance in patients with idiopathic growth hormone deficiency (IGHD), the MR imagings of 26 patients with IGHD were analyzed. On MRI, 24 out of 26 cases (92. 3%) showed apparent pituitary upper margin depresslon t 8 out of 26 cases (30. 8%) showed defmlte pituitary stalk transeetlon; 22 out of 26 cases (84. 6%) showed absence of the normal posterior pituitary bright spot. The bright lipidlike signal on TIW1 images at the median eminence distal to the breaking point (so-called ectople posterior lobe) was found in 4 out of 26 cases (15.4%). According to the MRI findings of iehe pituitary stalks, the 26 cases were divided into three groups; group A of 8 cases (31%) characterized by the definite transaction of stalk; group B of 13 cases (50%) defined by the possible stalk transection; and group C of 5 eases (19%) with no definite stalk transection. MRI findings were consistent with the clinical and endocrine tests. The stalk transection was staristically significantly difference in insulin test, L-dopa/p test, and height standard deviation score (P<0. 05). The MRI of hypothalamic-pltuitary area may differentiate partial IGHD form stalk-transected,doubtful transection and without transection.

Expression of hippocampal corticosteroid receptors,as well as corticotrophin-releasing hormone and vasopressin in the hypothalamic paraventricular nucleus,in fornix transected rats

BACKGROUND： The hippocampus regulates the hypothalamic-pituitary-adrenal axis through negative feedback. The hypothalamic paraventricular nucleus receives neuronal input from the hippocampus via the fomix, OBJECTIVE： To explore whether the negative feedback effect of the hippocampus on the hypothalamic-pituitary-adrenal axis is contributed to the inhibitory effect of mineralocorticoid receptor （MR） and glucocorticoid receptor （GR） in the hippocampus on the paraventricular nucleus via the fornix. DESIGN, TIME AND SETTING： Randomized, controlled, animal experiment. The study was performed at the Department of Histology and Embryology, China Medical University between September 2006 and September 2008. MATERIALS： Rabbit anti-rat anti-MR and rabbit anti-rat anti-GR antibodies were purchased from Santa Cruz Biotechnology, USA. Rabbit anti-rat anti-corticotrophin releasing hormone （CRH） and rabbit anti-rat anti-arginine vasopressin antibodies were purchased from Wuhan Boster. METHODS： A total of 90 male, Wistar rats were randomly divided into model and sham-surgery groups （n = 45）. Fornix transection was performed in the model group, while the sham-surgery group underwent surgery, but no fornix transection. MAIN OUTCOME MEASURES： Immunohistochemistry was used to examine MR and GR expression in the hippocampus, as well as CRH and anti-arginine vasopressin in the paraventricular nucleus. Western blot was used to measure alterations in MR, GR, and CRH protein expression following fomix transection. RESULTS： Compared with the sham-surgery group, there were no obvious changes in MR and GR expression in the hippocampus, or CRH and anti-arginine vasopressin expression in the paraventdcular nucleus within 4 days of fornix transection. However, after 7-10 days, significantly decreased MR and GR expression in the hippocampus, and increased CRH and anti-arginine vasopmssin expression in the paraventricular nucleus were observed （P 〈 0.05-0.01）. CONCLUSION： Negative feedback from the hippocampus on the hypothalamic-pituitary-adrenal axis might be mediated through the fornix, and the corticosterene actions mediated by hippocampal corticosteroid receptors indirectly modulated the hypothalamic-pituitary-adrenal axis.

Molecular mechanism of noradrenaline during the stress-induced major depressive disorder

Chronic stress-induced depression is a common hallmark of many psychiatric disorders with high morbidity rate.Stress-induced dysregulation of noradrenergic system has been implicated in the pathogenesis of depression.Lack of monoamine in the brain has been believed to be the main causative factor behind pathophysiology of major depressive disorder（MDD） and several antidepressants functions by increasing the monoamine level at the synapses in the brain.However,it is undetermined whether the noradrenergic receptor stimulation is critical for the therapeutic effect of antidepressant.Contrary to noradrenergic receptor stimulation,it has been suggested that the desensitization of β-adrenoceptor is involved in the therapeutic effect of antidepressant.In addition,enhanced noradrenaline（NA） release is central response to stress and thought to be a risk factor for the development of MDD.Moreover,fast acting antidepressant suppresses the hyperactivation of noradrenergic neurons in locus coeruleus（LC）.However,it is unclear how they alter the firing activity of LC neurons.These inconsistent reports about antidepressant effect of NA-reuptake inhibitors（NRIs） and enhanced release of NA as a stress response complicate our understanding about the pathophysiology of MDD.In this review,we will discuss the role of NA in pathophysiology of stress and the mechanism of therapeutic effect of NA in MDD.We will also discuss the possible contributions of each subtype of noradrenergic receptors on LC neurons,hypothalamic-pituitary-adrenal axis（HPA-axis） and brain derived neurotrophic factor-induced hippocampal neurogenesis during stress and therapeutic effect of NRIs in MDD.

EFFECT OF ACUPUNCTURE ON WEIGHT LOSS EVALUATED BY ADRENAL FUNCTION

In order to understand the relationship between patients’adrenal function and simple obesity andeffect of acupuncture on it,the obesity indices,lipid indices,fasting blood-glucose,noradrenalin,dopamine,adrenalin and cortisol were observed.The results indicated that patients with simpleobesity had hypofunction of the sympathetic-adrenal system and the hypothalamus-pituitary-adrenal system.Acupuncture treatment not only affected weight loss but also enhanced func-tioning of the two systems,suggesting that the effect of acupuncture on weight loss may be pro-duced by enhancing the functions of both the sympathetic-adrenal system and thehypothalamus-pitnitary-adrenal system.

Reversing the negative effects of co-inhaled manganese and iron on dopamine levels and prolactin production in the rat hypothalamus-pituitary axis

BACKGROUND： Manganese （Mn） and iron （Fe） are the primary elements of welding rods. Mn has been shown to increase prolactin （PRL） production by decreasing dopamine （DA） levels in the hypothalamus. However, Fe increases DA levels and decreases PRL levels. The toxic mechanism of Mn and Fe co-inhalation-induced regulation of the hypothalamic-hypophyseal-pituitary axis remains unclear. OBJECTIVE： To evaluate the effects of co-inhaled Mn and Fe on hypothalamic DA levels and pituitary PRL production, to investigate whether these changes are reversible, and to determine the role of co-inhaled Mn and Fe. DESIGN, TIME AND SETTING： A randomized, controlled, animal experiment based on inhalation toxicity via whole-body exposure was performed. Hypothalamic DA levels, serum PRL, and PRL and PiN mRNA levels were analyzed at the Institute of Environmental and Occupational Medicine, Inje University, Busan, Korea, from August 2007 to May 2009. MATERIALS： MnSO4 and FeSO4 were purchased from Sigma-Aldrich, St. Louis, MO, USA. High-performance liquid chromatography （HPLC） using an electrochemical detector （ECD） was purchased from Waters Corporation, Milford, MA, USA. mRNA Capture Kit and reverse transcription-polymerase chain reaction （RT-PCR） kit were obtained from Roche Molecular Biochemicals, Mannheim, Germany and Perkin-Elmer, Wellesley, MA, USA, respectively. Rat PRL enzyme-linked immunosorbent assay kit was purchased from Biocode Hycel, Liege, Belgium. METHODS： Eighty 15-week-old, male, Fischer 344 rats were assigned to two groups： one group treated with Mn and Fe and a control group. Each group was sub-divided into four groups on the basis of treatment period （0- and 13-week treated groups with both chemicals） and recovery periods （4- and 13-week recovery groups following 13-week exposure to both chemicals）. The treatment condition was 6 hours per day, 5 days per week, for the entire body. Mn and Fe co-inhalation concentrations were 1.5 mg/m3 and 3.0 mg/m3, respectively. MAIN OUTCOME MEASURES： Hypothalamic DA levels were measured using HPLC-ECD analysis mRNA levels of PRL and Pit-1 were analyzed by Northern blot hybridization and RT-PCR, respectively. Serum PRL levels were measured by enzyme-linked immunosorbent assay. RESULTS： HPLC-ECD analysis revealed that following 13-week co-inhalation of Mn and Fe, hypothalamic DA levels significantly deceased, whereas pituitary PRL mRNA, Pit-1 mRNA, and serum PRL levels significantly increased. At 4 weeks of recovery, DA level in the hypothalamic tissue was significantly increased, and PRL and Pit-1 mRNA levels in the pituitary were significantly decreased. After 13 weeks of recovery, DA and PRL levels recovered to normal. The changing pattern of serum PRL levels was in accordance with pituitary PRL mRNA levels. CONCLUSION： Subchronic co-inhalation of Mn and Fe significantly decreased hypothalamic DA levels, but induced pituitary PRL production, both of which were mediated by Pit-1. These results suggested that Mn dominates over Fe in terms of hypothalamic DA levels and pituitary PRL production, and these effects are reversible in a subchronic inhalation condition. Therefore, changes in hypothalamic DA levels and serum PRL production could be used as biomarkers for welders, who are exposed to Mn and Fe.

青少年非自杀性自伤患者自杀未遂与HPT轴和HPA轴功能改变的研究

目的探讨伴非自杀性自伤(non-suicidal self-injury,NSSI)行为的青少年心境障碍患者发生自杀未遂(suicide attempt,SA)与下丘脑-垂体-甲状腺(hypothalamic-pituitary-thyroid,HPT)轴功能和下丘脑-垂体-肾上腺(hypothalamic-pituitary-adrenal,HPA)轴功能改变的相关性。方法选取2020年12月至2022年5月在首都医科大学附属北京安定医院住院的近1年有NSSI史的13~19岁青少年心境障碍患者进行横断面调查,根据近一年是否存在SA将患者分为非SA组和SA组。根据SA发生的时间段(1个月)将SA组患者分为近期SA和既往SA。收集患者临床特征、甲状腺功能[游离三碘甲状腺原氨酸(free triiodothyronine,FT3)、游离甲状腺素(free thyroxine,FT4)、总三碘甲状腺原氨酸(total triiodothyronine,TT3)、总甲状腺素(total thyroxine,TT4)、促甲状腺激素(thyroid stimulating hormone,TSH)]及促肾上腺皮质激素(adrenocorticotropin,ACTH)、皮质醇(cortisol,CORT)水平。采用多因素Logistic回归分析SA的影响因素。结果共入组79例伴NSSI青少年心境障碍患者,其中49例(62.03%)发生SA,其中29例(59.18%)患者为近1个月内发生SA。单因素分析显示,SA组和非SA组患者在首次发病年龄、性别、教育水平方面差异有统计学意义(P<0.05)。近期SA组患者和既往SA组患者在年龄、TSH、ACTH水平存在差异(P<0.05)。Logistic回归分析显示,女性(P=0.027,OR=2.941,95%CI:1.131~7.649)是患者发生SA的独立危险因素,ACTH水平降低(P=0.043,OR=1.019,95%CI:1.001~1.037)是近期发生SA的相关因素。结论女性伴NSSI青少年心境障碍患者易发生SA,ACTH水平低是近期发生SA的危险因素。

柴胡疏肝散合半夏厚朴汤联合五行针灸对脑卒中后焦虑抑郁的神经调控作用及对免疫炎症反应、认知功能损害和HPG、HPT的影响

目的:观察柴胡疏肝散合半夏厚朴汤联合五行针灸对脑卒中后焦虑抑郁患者的神经调控作用及对免疫炎症反应、认知功能损害和下丘脑-垂体-性腺轴(HPG)、下丘脑-垂体-甲状腺轴(HPT)的影响。方法:选择2021年3月至2023年5月于该院治疗的脑卒中后焦虑抑郁患者102例,根据随机数字表法分组,其中五行针灸组51例(脱落2例,最终纳入49例),方剂联合组51例(脱落2例,最终纳入49例)。两组患者同时给予常规西医基础治疗,五行针灸组患者在常规西医基础治疗的基础上给予五行针灸治疗,方剂联合组患者在五行针灸组的基础上给予柴胡疏肝散合半夏厚朴汤治疗。观察两组患者的临床疗效,比较患者治疗前后的中医证候评分、简易精神状态量表(MMSE)评分、广泛性焦虑障碍量表(GAD-7)评分、汉密顿抑郁量表(HAMD)评分和简明幸福与生活质量满意度问卷(Q-LES-Q-SF)评分,检测患者治疗前后血清神经生长因子(NGF)、白细胞介素1β(IL-1β)、胶质纤维酸性蛋白(GFAP)、白细胞介素17a(IL-17a)、促甲状腺激素(TSH)、5-羟色胺(5-HT)和雌二醇(E2)水平。结果:方剂联合组患者的总有效率为97.96%(48/49),高于五行针灸组的81.63%(40/49),差异有统计学意义(P<0.05)。治疗后,方剂联合组患者精神焦虑抑郁、脘痞、胸胁作胀、善太息和嗳气频作等中医证候评分较五行针灸组降低,HAMD、GAD-7评分较五行针灸组降低,MMSE、Q-LES-Q-SF评分较五行针灸组升高,差异均有统计学意义(P<0.05)。治疗后,方剂联合组患者的IL-1β、IL-17a和GFAP水平较五行针灸组降低,NGF水平较五行针灸组升高,5-HT、E2和TSH水平较五行针灸组升高,差异均有统计学意义(P<0.05)。结论:柴胡疏肝散合半夏厚朴汤联合五行针灸治疗脑卒中后焦虑抑郁患者,可减少免疫炎症反应,减少神经及认知功能损害,调节HPG、HPT,改善焦虑及抑郁情绪,缓解病情,提高生活质量及临床疗效。

基于下丘脑-垂体-肾上腺轴探讨电针对功能性消化不良大鼠的作用机制

目的探讨电针印堂、内关、足三里对FD大鼠下丘脑-垂体-肾上腺轴的可能作用机制。方法40只SD大鼠随机分为空白组、模型组和电针组。采用夹尾、不规律饮食以及冰生理盐水灌胃法复制FD模型。造模后,电针组行针刺干预,每天1次,每次30 min,连续14天。记录大鼠的一般状态;旷场实验检测大鼠的自主行为及紧张度;HE染色法观察大鼠胃黏膜形态及炎症反应;实时荧光定量PCR法检测大鼠下丘脑5-羟色胺3受体(5-HT3R)、促肾上腺皮质激素释放激素(CRH)的表达;蛋白免疫印迹法检测大鼠十二指肠促肾上腺皮质激素释放激素受体2(CRHR2)、NOD样受体蛋白6(NLRP6)蛋白表达;阿利新蓝染色观察大鼠十二指肠黏膜上皮形态及杯状细胞的阳性表达。结果与空白组相比,模型组大鼠一般状态、旷场自主运动距离、运动速度、十二指肠CRHR2、NLRP6蛋白均大幅下降(P<0.05),下丘脑5-HT3R、CRH mRNA明显升高(P<0.05)。与模型组相比,电针组大鼠一般状态、旷场自主运动距离、运动速度、十二指肠CRHR2、NLRP6蛋白及杯状细胞的表达均明显提高(P<0.05),下丘脑5-HT3R、CRH mRNA大幅下降(P<0.05)。模型组大鼠胃黏膜可见疏松的结缔组织,黏膜下层轻度水肿,淋巴细胞增生;空白组和电针组大鼠胃黏膜结缔组织排列紧密,胃腺间质无明显增生,未见炎症细胞。结论电针印堂、内关、足三里可能是通过提升十二指肠CRHR2、NLRP6蛋白和杯状细胞表达,抑制下丘脑5-HT3R、CRH的表达,来提高FD大鼠自主运动水平,缓解焦虑,修复缺损的肠道黏膜屏障,恢复下丘脑-垂体-肾上腺轴的正常功能。

Inflammatory airway features and hypothalamic-pituitary- adrenal axis function in asthmatic rats combined with chronic obstructive pulmonary disease

Background Bronchial asthma （BA） and chronic obstructive pulmonary disease （COPD） are both inflammatory airway diseases with different characteristics. However, there are many patients who suffer from both BA and COPD. This study was to evaluate changes of inflammatory airway features and hypothalamic-pituitary-adrenal （HPA） axis function in asthmatic rats combined with COPD. Methods Brown Norway （BN） rats were used to model These three models were compared and evaluated with the inflammatory airway diseases of BA, COPD and COPD＋BA. respect to clinical symptoms, pulmonary histopathology, airway hyperresponsiveness （AHR）, inflammatory cytokines and HPA axis function. Results The inflammatory airway features and HPA axis function in rats in the COPD＋BA model group were greatly influenced. Rats in this model group showed features of the inflammatory diseases BA and COPD. The expression of inflammatory cytokines in this model group might be up or downregulated when both disease processes are present. The levels of corticotrophin releasing hormone mRNA and corticosterone in this model group were both significantly decreased than those in the control group （P 〈0.05）. Conclusions BN rat can be used as an animal model of COPD＋BA. By evaluating this animal model we found that the features of inflammation in rats in this model group seem to be exaggerated. The HPA axis functions in rats in this model group have been disturbed or impaired, which is prominent at the hypothalamic level.