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 rain 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-rTMS 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）

Shizhenqing granule stimulates the hypothalamic-pituitary-adrenal axis and reduces serum pro-inflammatory factors in a rat model with chronic eczema

Objective:In this study,we examined the effects of Shizhenqing granule(SZQG)on hypothalamicpituitary-adrenal(HPA)axis and serum inflammatory factors in a rat model of chronic eczema,in order to explore the mechanism of action of SZQG in treatment of this disease.Methods:Sixty SpragueeDawley male rats were randomly divided into six groups(with 10 rats per group):blank group;model group;positive control group(prednisone);and the low-,medium-,and high-dose SZQG groups.Except for the blank group,rats in all other groups were treated with 2,4-dinitrochlorobenzene to induce chronic eczema.These rats were administered prednisone or SZQG for 7 consecutive days after successful establishment of the chronic eczema model,and samples were collected 12 h after the last administration.The degree of skin lesions and the changes in serum levels of corticotropin-releasing hormone(CRH),adrenocorticotropic hormone(ACTH),cortisol(CORT),interleukin(IL)-4,interferon(IFN)-g,IL-25,and IL-31 among the groups were compared.Results:SZQG effectively increased the levels of CRH,ACTH,and CORT,which decreased in the serum of rats with chronic eczema,stimulated the function of the HPA axis,and promoted the expression of glucocorticoids.SZQG reduced the serum levels of inflammatory factors including IL-4,IL-25 and IL-31,which were overexpressed in rats with chronic eczema,and increased those of anti-inflammatory factor IFN-g,thereby alleviating the inflammatory symptoms and itching,and ameliorating the clinical symptoms of chronic eczema.Conclusion:SZQG effectively alleviates skin lesions in the chronic eczema rat model by stimulating the function of the HPA axis.

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.

Seasonal photoperiodic influence of pineal melatonin on hypothalamic-pituitary-adrenal axis-hippocampal-receptor in male rats

Background: Based on the effect of seasonal changes on human visceral function, this study investigated the impact of seasonal photoperiod of the pineal body on hypothalamic-pituitary-adrenal axis-hippocampal-receptor in rats, aiming to reveal the mechanism by which pineal gland melatonin regulates the seasonal secretion of hippocampal neurotransmitters.Methods: Vernal equinox, summer solstice, autumn equinox, and winter solstice were selected as four experimental time points, and rats were randomly divided into normal control group, sham operation group, and pinealectomized group. The seasonal changes in corticotropin-releasing hormone(CRH),adrenocorticotropic hormone(ACTH), corticosterone, hypothalamic melatonin receptor(MTR), and hippocampal corticosterone receptor(CORTR) were examined by enzyme-linked immunosorbent assay.Results: Comparing the same group between different seasons, we showed that in the normal control group, CRH, ACTH, corticosterone, and MTR were higher, while CORTR was lower in autumn and winter than in spring(all P <.05). Compared with the normal control group, the pinealectomized group showed higher levels of corticosterone(P =.01), MTR(P =.01), and CORTR(P =.03) during spring;reduced levels of MTR and CORTR(both P <.001) during summer;higher levels of ACTH(P =.001) and MTR(P <.001),and lower levels of CRH(P =.001), corticosterone(P <.001), and CORTR(P =.003) during autumn;and lower levels of CRH(P <.001) and MTR(P =.004), and higher level of ACTH(P <.001) in winter.Conclusions: Seasonal photoperiod acts on the pineal gland to secrete different levels of melatonin,resulting in seasonal changes in the hypothalamic-pituitary-adrenal axis-hippocampal-receptor, which may be the pathophysiological basis for the onset of seasonal affective disorder.

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.

基于ARM Cortex-M3的舰用无线振动检测系统

为了满足舰船上振动检测的需求,开发一种以ARM Cortex-M3内核的32位微控制器为核心的无线振动检测系统。介绍了有无线传输功能,由检测节点,汇聚节点和上位机组成的三层结构设计方案。设计了各个节点中三轴加速度传感器、无线传输、通信接口等模块的硬件电路,并给出了各个节点和上位机的控制、通讯的软件设计方案。实际测试表明,此系统具有操作安装简单、实时性强、低功耗、低成本等特点,应用前景广泛。

Glucocorticoid receptor signaling in the brain and its involvement in cognitive function

The hypothalamic-pituitary-adrenal axis regulates the secretion of glucoco rticoids in response to environmental challenges.In the brain,a nuclear receptor transcription fa ctor,the glucocorticoid recepto r,is an important component of the hypothalamicpituitary-a d renal axis's negative feedback loop and plays a key role in regulating cognitive equilibrium and neuroplasticity.The glucoco rticoid receptor influences cognitive processes,including glutamate neurotransmission,calcium signaling,and the activation of brain-derived neurotrophic factor-mediated pathways,through a combination of genomic and non-genomic mechanisms.Protein interactions within the central nervous system can alter the expression and activity of the glucocorticoid receptor,there by affecting the hypothalamic-pituitary-a d renal axis and stress-related cognitive functions.An appropriate level of glucocorticoid receptor expression can improve cognitive function,while excessive glucocorticoid receptors or long-term exposure to glucoco rticoids may lead to cognitive impairment.Patients with cognitive impairment-associated diseases,such as Alzheimer's disease,aging,depression,Parkinson's disease,Huntington's disease,stroke,and addiction,often present with dysregulation of the hypothalamic-pituitary-adrenal axis and glucocorticoid receptor expression.This review provides a comprehensive overview of the functions of the glucoco rticoid receptor in the hypothalamic-pituitary-a d renal axis and cognitive activities.It emphasizes that appropriate glucocorticoid receptor signaling fa cilitates learning and memory,while its dysregulation can lead to cognitive impairment.This provides clues about how glucocorticoid receptor signaling can be targeted to ove rcome cognitive disability-related disorders.

基于飞思卡尔Cortex-M0＋微控制器的计步器设计

为了满足现代日益增长的健康减肥要求,文中以Cortex-M0+内核的32位微控制器MKL25Z为微处理器,采用分辨率高、反应速度快、功耗低的三轴加速度传感器MMA8451Q,设计了一款嵌入式智能化计步器。运用液晶图形化显示技术,电容触摸按键输入,测量和控制数据处理技术,网络通信技术等,加入嵌入式系统的应用,实现了仪表的智能化、信息化和网络化。实践证明其满足了实用性和可靠性的功能要求。

Essence of"Shen(Kidney)Controlling Bones":Conceptual Analysis Based on Hypothalamic-Pituitary-Adrenal-Osteo-Related Cells Axis

As a traditional concept of Chinese medicine（CM）, the theory of ＂Shen（Kidney） controlling bones＂ has been gradually proven. And in modern allopathic medicine, the multiple mechanisms of bone growth, development and regeneration align with the theory. Shen deficiency as a pathological condition has a negative effect on the skeleton of body, specifically the disorder of bone homeostasis. Present studies indicate that Shen deficiency shares a common disorder characterized by dysfunction of hypothalamic-pituitary-adrenal（HPA） axis. HPA axis may be an important regulator of bone diseases with abnormal homeostasis. Therefore, we posit the existence of hypothalamic-pituitary-adrenal-osteo-related cells axis： cells that comprise bone tissue（osteo-related cells） are targets under the regulation of HPA axis in disorder of bone homeostasis. Chinese herbs for nourishing Shen have potential in the development of treatments for disorder of bone homeostasis.

Functional changes in the hypothalamic-pituitary-adrenal axis after successful cardiopulmonary resuscitation

Background:Cardiac arrest(CA)is a terminal event that results in a range of pathophysiological changes in the body,most notably,systemic ischemia-reperfusion injury.The hypothalamic-pituitary-adrenal(HPA)axis is an important neuroendocrine system that modulates adrenocortical hormone release.This study was designed to investigate the changes in HPA-related hormone levels after successful cardiopulmonary resuscitation(CPR)and to explore possible etiologies to provide a basis for relevant clinical research.Methods:We collected the clinical data of 96 patients with CA admitted to the Emergency Department of Beijing Chaoyang Hospital,Capital Medical University,between January 2016 and May 2017.Serum samples were collected 6,24,and 72 hours after restoring spontaneous circulation(ROSC).The data were compared with those of the healthy control group(n=50).An enzyme-linked immunosorbent assay(ELISA)was performed to measure copeptin,adrenocorticotropic hormone(ACTH),corticotropin-releasing hormone(CRH),and total cortisol.Demographic data were collected for both groups.For the CPR group,clinical data and the end-of-study cerebral performance category(CPC)were analyzed.Patients were followed up through day 28.Death or survival after day 28 was used as the study endpoint.Simple values were expressed as medians and quartiles or ratios(%)for statistical analysis.Continuous variables are expressed as mean±standard deviation.Categorical variables were expressed as frequencies and percentages.The mean values of normally distributed measurement data were analyzed using 1-way analysis of variance(ANOVA)for among-group comparisons and the least significant difference(LSD)test for between-group comparisons.SPSS v17(SPSS,Chicago,IL,USA)was used for statistical analysis,and P<0.05 was considered statistically significant.Results:No significant between-group differences were observed in terms of age or sex.The 28-day mortality rate in the CPR group was 71%.ACTH and CRH levels were significantly lower in the CPR group than in the healthy control group(P<0.001).Copeptin and cortisol levels 6 hours after ROSC were significantly higher in the CPR group than in the healthy control group(P<0.001).No significant changes in any indicator were observed over time(6,24,and 72 hours after ROSC)(P>0.05).The CPC score was 1–2(good cerebral performance group)in 13 patients,3–4(poor cerebral performance group)in 17 patients,and 5(brain death or clinical death)in 66 patients.Patients with significantly declining ACTH and CRH levels had higher CPC scores(P<0.05);however,no significant differences were found in other indicators(P>0.05).Conclusion:After post-CA ROSC,ischemia-reperfusion injury may cause brain damage and HPA axis damage and dysfunction,the severity of which is associated with CPC score.

有氧运动通过“脑-心”轴抑制交感神经过度激活改善心肌梗死小鼠心功能

目的:探讨有氧运动改善心肌梗死小鼠心功能的中枢机制。方法:C57BL/6J小鼠随机分为假手术组(Sham)、心肌梗死组(MI)、心肌梗死运动组(ME),每组12只;光遗传激活组(ChR2)、光遗传抑制组(eNpHR3.0),每组6只;心肌梗死对照组(MI+Dio)、心肌梗死+初级运动皮层(primary motor cortex,M1)区神经元消融组(MI+taCasp3),每组6只。采用左冠状动脉前降支结扎术制备心肌梗死模型,术后1周对ME组进行6周有氧运动干预。心脏注射伪狂犬病病毒(pseudorabies virus,PRV)逆行跨多突触标记,以解析中枢与心脏的神经通路。通过光遗传激活或抑制初级运动皮层M1区谷氨酸(Glutamate,Glu)能神经元,以及神经元消融技术沉默初级运动皮层M1区Glu能神经元,探究初级运动皮层M1区Glu能神经元对心脏交感神经活动的影响。采用Masson和苏木精-伊红染色评估心脏结构病理变化,心电图检测心率变异性,心动超声评定心功能,试剂盒检测血清去甲肾上腺素(norepinephrine,NE)含量。利用Western blot和免疫荧光检测心脏的交感神经标记物酪氨酸羟化酶(tyrosine hydroxylase,TH)、神经生长因子(neu‐rotrophic factor,NGF)、生长相关蛋白43(growth-associated protein 43,GAP43)的表达,以及M1区神经元裂解型半胱氨酸蛋白酶-3(c-Caspase3)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、白细胞介素-6(interleukin 6,IL-6)蛋白表达。采用尼氏染色和微管关联蛋白2(microtubule associated protein 2,MAP-2)免疫荧光染色评估神经元损伤。利用电镜观察初级运动皮层M1区神经元超微结构。结果:左心室注射PRV 5.5天后在正常小鼠初级运动皮层M1区第五层(L5)观察到大量被标记的神经元。光遗传激活或抑制初级运动皮层M1区Glu能神经元,显著升高或降低心率变异性指标低频和高频功率比值(LF/HF)。与MI+Dio组比较,MI+taCsap3组血清NE含量、LF/HF功率比值以及心肌梗死边缘区TH、GAP43和NGF表达显著降低。与Sham组比较,MI组初级运动皮层M1区神经元MAP-2表达降低,Nissl小体密度降低,线粒体出现肿胀、分裂,嵴溶解等超微结构病理改变,c-Caspase3表达显著增加,TNF-α和IL-6表达增加,而有氧运动干预显著逆转该变化。与Sham组比较,MI组LF/HF功率比值显著升高,心肌NGF和TH分布面积、密度以及心肌胶原纤维显著增加,心功能降低,有氧运动干预显著逆转该变化。结论:由于支配心脏活动的神经元链与大脑初级运动皮层M1区Glu能神经元存在投射,抑制大脑初级运动皮层M1区Glu能神经元活动,显著改善心肌梗死后交感神经过度激活和心脏恶性重构。有氧运动可显著改善心肌梗死后大脑初级运动皮层M1区神经元损伤,抑制心交感神经恶性重构,改善心功能。提示,聚焦大脑初级运动皮层M1区神经调控与心脏保护,可能为未来研究无创治疗或预防心肌缺血损伤提供新的思路。

Effects of acupuncture on hypothalamic–pituitary–adrenal axis:Current status and future perspectives

The hypothalamic–pituitary–adrenal(HPA) axis is a critical component of the neuroendocrine system,playing a central role in regulating the body's stress response and modulating various physiological processes. Dysregulation of HPA axis function disrupts the neuroendocrine equilibrium, resulting in impaired physiological functions. Acupuncture is recognized as a non-pharmacological type of therapy which has been confirmed to play an important role in modulating the HPA axis and thus favorably targets diseases with abnormal activation of the HPA axis. With numerous studies reporting the promising efficacy of acupuncture for neuroendocrine disorders, a comprehensive review in terms of the underlying molecular mechanism for acupuncture, especially in regulating the HPA axis, is currently in need. This review fills the need and summarizes recent breakthroughs, from the basic principles and the pathological changes of HPA axis dysfunction, to the molecular mechanisms by which acupuncture regulates the HPA axis. These mechanisms include the modulation of multiple neurotransmitters and their receptors, neuropeptides and their receptors, and microRNAs in the paraventricular nucleus,hippocampus, amygdala and pituitary gland, which alleviate the hyperfunctioning of the HPA axis.This review comprehensively summarizes the mechanism of acupuncture in regulating HPA axis dysfunction for the first time, providing new targets and prospects for further exploration of acupuncture.

肾阳虚大鼠垂体-肾上腺皮质轴与垂体-性腺轴相关性研究

目的了解肾阳虚大鼠垂体-肾上腺皮质轴及垂体-性腺轴功能之间的相互关系。方法肌肉注射氢化可的松复制肾阳虚大鼠模型,采用分批宰杀的方法观察早期、中期和晚期肾阳虚大鼠垂体-肾上腺皮质轴及垂体-性腺轴功能指标,对测试数据进行相关性分析,探讨垂体-肾上腺皮质轴及垂体-性腺轴之间的变化规律和特征。结果正常组垂体-性腺轴激素中早期T与FSH有相关性且为负相关,晚期CORT与ACTH有正相关,模型组早期ACTH与LH有显著负相关,模型组中期FSH与LH有显著正相关性,CORT与T有正相关性。结论肾阳虚早期时垂体-肾上腺皮质轴与垂体-性腺轴的垂体激素有负相关性,即二轴存在相互抑制作用;但中期时靶腺的激素有正相关性,表现为平行关系,二轴同时受损;证实肾阳虚是一种综合的动态且可转化的功能态。

淫羊藿苷对维生素D缺乏大鼠肾上腺皮质维生素D轴及VDR蛋白表达的影响

目的：观察淫羊藿苷对维生素D缺乏大鼠肾上腺皮质维生素D轴的影响。方法：选用60只雄性SD大鼠,随机分为：正常组;模型组（生理盐水4.0 mL·kg-1·d-1灌胃）;淫羊藿苷高剂量组（120 mg·kg-1·d-1灌胃）;淫羊藿苷中剂量组（60 mg·kg-1·d-1灌胃）;淫羊藿苷低剂量组（30 mg·kg-1·d-1灌胃）;维生素D组（30ng·kg-1·d-1灌胃）。造模1月后,药物干预2月,酶联免疫法（ELISA法）检测血清25（OH）D3、1,25（OH）D3。免疫组化检测VDR蛋白表达。Real-Time PCR法检测肾上腺皮质维生素D受体（VDR）、25-羟维生素D3-24-羟基化酶（CYP24A1）、25-羟维生素D1α-羟化酶（CYP27B1）mRNA表达。结果：与正常组比较,模型组血清25（OH）D3、1,25（OH）D3含量下降（P〈0.05）;淫羊藿苷干预后血清25（OH）D3、1,25（OH）D3含量均上升（P〈0.05）。免疫组化显示,与正常组比较,模型组VDR蛋白表达下降（P〈0.05）;经淫羊藿苷干预后,表达上升（P〈0.05）。Real-Time PCR显示,经淫羊藿苷干预后,表达量上调（P〈0.05）,除VDRmRNA外,CYP24A1mRNA与CYP27B1mRNA变化趋势均与维生素D组表现一致。模型组基因表达均高于正常组（P〈0.05）,Real-Time PCR检测结果与免疫组化检测的蛋白表达不完全一致。结论：淫羊藿苷可能调节维生素D轴促进VDR蛋白表达改善维生素D缺乏。

镉致腺垂体-肾上腺皮质凋亡机制研究

目的观察CdCl2作用后腺垂体-肾上腺皮质系统凋亡情况及半胱天冬酶-9的表达变化。方法48只雄性SD大鼠随机分为4组,即对照组、CdCl2低剂量组(1.0 mg/kg)、中剂量组(2.0 mg/kg)、高剂量组(4.0 mg/kg)。经口灌胃染毒,每周5 d,连续6周。染毒结束后分离腺垂体和肾上腺皮质进行透射电镜观察、末端脱氧核苷酸转移酶介导的dUTP缺口末端标记法(TUNEL)检测细胞凋亡、半胱天冬酶原-9mRNA(procaspase-9mRNA)表达、半胱天冬酶-9(caspase-9)表达。结果电镜检查可见凋亡细胞早期形态学变化;中、高剂量组腺垂体和肾上腺TUNEL阳性细胞的平均灰度值和procaspase-9 mRNA阳性细胞相对灰度值均为对照组的1.2倍以上(P<0.05);蛋白印迹(westernboltting)结果显示,随着染毒剂量的增加,垂体-肾上腺系统caspase-9表达逐渐增强(P<0.01)。结论CdCl2可诱发腺垂体-肾上腺皮质细胞凋亡,在此过程中caspase-9及其酶原mRNA表达呈现出与凋亡较为一致的趋势。

基于维生素D轴探讨黄芪多糖对脓毒症肾上腺皮质功能的保护机制

脓毒症(sepsis)是一种具有全身性的炎症反应综合征,常并发于严重创伤、烧伤、感染及大手术等多种应激情况,易诱发脓毒症休克及多器官功能障碍综合征(MODS)。肾上腺皮质功能不全是脓毒症的重要病理改变。另一方面,维生素D不仅与脓毒症密切相关,还对肾上腺皮质功能存在一定调控作用。此外,黄芪多糖可改善脓毒症。基于文献及前期研究表明黄芪具有调节维生素D轴的作用,黄芪多糖具有调节肾上腺皮质的功能,据此提出黄芪多糖可能通过作用于维生素D轴,调节肾上腺皮质功能,从而改善脓毒症。

ACTH和槐杞黄治疗频复发肾病综合征患儿的疗效观察

目的观察促肾上腺皮质激素(ACTH)联合槐杞黄对频复发肾病综合征(FRNS)患儿的疗效及安全性。方法55例FRNS患儿分为糖皮质激素(GC)维持治疗的对照组(A组,10例)、槐杞黄组(B组,17例)、ACTH组(C组,14例)和ACTH联合槐杞黄组(联合治疗组,D组,14例),连续治疗12个月。分别记录治疗6个月和12个月时各组GC使用量、肾上腺皮质基础分泌水平及肾上腺皮质储备水平,同时记录各组患儿复发率及不良反应情况。结果治疗6个月后,C、D组的GC用量明显低于A、B组(P<0.05),A^D组肾上腺皮质储备水平依次升高(P<0.05)。治疗12个月后,C、D组与A、B组相比较,GC用量降低,肾上腺皮质基础分泌水平和储备水平均升高(P<0.05),而C、D组间上述指标差异无统计学意义(P>0.05)。在治疗6个月和12个月后,C、D组患儿复发率均低于A、B组(P<0.05)。结论单纯应用ACTH以及联合槐杞黄均可减轻FRNS患儿长期服用GC对下丘脑-垂体-肾上腺轴的抑制作用。

美替拉酮阻断下丘脑-垂体-肾上腺皮质轴及加味逍遥丸对慢性心理应激小鼠免疫系统的影响

目的探讨美替拉酮阻断下丘脑-垂体-肾上腺皮质轴(hypothalamic-pituitary-adrenalcortexaxis,HPAA)对慢性心理应激小鼠免疫器官和细胞免疫功能有无保护作用,以及加味逍遥丸调节慢性心理应激损伤的作用是否与下丘脑-垂体-肾上腺皮质轴相关。方法将小鼠随机分为生理盐水对照组、加味逍遥丸对照组、美替拉酮对照组、美替拉酮合用加味逍遥丸对照组、生理盐水应激组、加味逍遥丸应激组、美替拉酮应激组、美替拉酮合用加味逍遥丸应激组。其中对照组小鼠不予以应激刺激,应激组小鼠采用电刺激条件反射箱诱导建立慢性心理应激模型。检测各组小鼠体质量、血清糖皮质激素水平、胸腺指数、胸腺细胞凋亡率、脾脏自然杀伤细胞活性及淋巴细胞转化率,并观察小鼠胸腺组织病理学改变。结果各应激组与其相对应的非应激对照组比较,其胸腺指数明显下降,自然杀伤细胞活性及淋巴细胞转化率均明显下降;同时,胸腺细胞凋亡率升高,胸腺组织病理损伤加重。美替拉酮及加味逍遥丸应激组与生理盐水应激组比较,其血清糖皮质激素含量明显下降,自然杀伤细胞活性及脂多糖刺激的淋巴细胞转化率明显升高,胸腺组织病理损伤减轻。美替拉酮合用加味逍遥丸应激组与单纯的美替拉酮或加味逍遥丸应激组各项指标比较,均无明显差异。结论阻断HPAA对慢性心理应激小鼠的免疫系统有明显的保护作用。加味逍遥丸对慢性心理应激小鼠的保护作用与美替拉酮阻断HPAA的效应基本一致,两者无叠加、协同效应。推测HPAA是加味逍遥丸抗应激损伤的作用靶点之一。

右归丸对肾阳虚模型大鼠下丘脑-垂体-肾上腺轴的影响

目的:探讨右归丸对肾阳虚模型大鼠下丘脑-垂体-肾上腺轴的影响。方法:将60只健康雄性SD大鼠随机分为右归丸组、模型组和空白组,每组20只。右归丸组大鼠接受肾阳虚模型制备后予右归丸灌胃给药干预;模型组大鼠接受肾阳虚模型制备后接受右归丸组同体积的0.9%NaCl灌胃,连续灌胃20 d;空白组大鼠不接受造模制备,第16日起同右归丸组同体积的0.9%Nacl灌胃,连续灌胃20日。造模结束后每隔4日常规记录大鼠体质量、肛温、饮水量、尿量、以及抓取激惹反应。比较3组大鼠促肾上腺皮质激素释放因子(CRF)、促肾上腺皮质激素(ACTH)、大鼠皮质醇(CORT)、促肾上腺皮质激素释放激素受体1(CRHR1)的含量变化。结果:1)造模后发现接受模型制备的大鼠表现为肛温降低,饮水量及摄食量减少,体质量下降,大便溏薄,尿量增多,抓取激惹反应减弱。进行药物干预后,右归丸组大鼠的肛温、饮水量、摄食量、抓取激惹反应、体质量均高于模型组比较,差异有统计学意义(P<0.05),尿量减少,且大便干湿趋于正常;2)与空白组比较模型组及右归丸组肾上腺、下丘脑、垂体的脏器指数均下降(P<0.05),其中模型组下降的趋势更为明显,右归丸组较模型组肾上腺、下丘脑、垂体的脏器指数有所上升(P<0.05);3)与空白组比较,模型组及右归丸组大鼠接受造模后血清CRF、ACTH、CORT以及肾上腺、下丘脑、垂体的CRHR1含量均明显下降,经过右归丸干预后,该组别的大鼠CRF、ACTH、CORT、CRHR1含量均得到提升,其中CRF、ACTH含量接近空白组水平。4)与空白组比较,模型组及右归丸组大鼠接受造模后肾上腺、下丘脑、垂体的CRF、ACTH、CORT及CRHR1 mRNA水平均明显下降,经过右归丸干预后,该组别的大鼠CRF、ACTH、CORT、CRHR1mRNA水平均得到提升。结论:右归丸可能是通过调节下丘脑-垂体-肾上腺皮质轴的功能发挥温肾补阳的作用。

雷公藤醋酸乙酯提取物对大鼠垂体的影响

雷公藤是一种有效的抗风湿中草药 ,临床和实验研究表明其具有多种药理学功能 .实验将 30只雄性 Sprague- Dawley大鼠完全随机分成雷公藤醋酸乙酯提取物 (TWEE)组 ,泼尼松组和对照组 .分别 ig给药 TWEE2 5mg·kg-1,每日 2次 ;泼尼松2 mg· kg-1,每日 2次和 0 .5%羧甲基纤维素钠 30d,所有大鼠于 d31断头处死 ,分离垂体和收集血液 .对垂体进行 HE和免疫细胞化学染色 ;应用放射免疫分析法检测血浆促肾上腺皮质激素 (ACTH)含量 .结果表明 TWEE能促进大鼠垂体远侧部ACTH细胞合成和分泌 ACTH.为临床综合评价雷公藤对下丘脑 -垂体 -肾上腺轴的影响提供了实验数据和理论依据 .