多发性硬化患者下丘脑-垂体-肾上腺轴功能改变的临床研究

目的：观察多发性硬化（multiple sclerosis ,MS）患者下丘脑‐垂体‐肾上腺轴（hypothalamo‐pituitary‐adrenal axis ,HPAA）的功能改变情况。方法选择作者医院60例非急性发作期MS患者（MS组）,以同期作者医院门诊健康体检者30名为健康对照（对照组）,采用酶联免疫吸附法（enzyme linked immunoassay ,ELISA ）检测早晨8点空腹血皮质醇（cortisol ,CORT ）、促肾上腺皮质醇激素（adrenocorticotropin ,ACT H ）、促肾上腺皮质醇激素释放激素（corticotropin releasing hormone ,CRH）水平。MS组患者根据EDSS评分的不同,分为EDSS＞4.5组（10例）和EDSS≤4.5组（50例）两组;根据 MS分型,分为复发缓解型 MS （relapsing‐remitting multiple sclerosis ,RRMS）组（48例）和非复发缓解型MS（非RRMS）组（12例）两组。结果与对照组〔（55.67±32.48） ng/mL〕比较,MS组CORT 〔（121.09±89.46） ng/mL〕表达升高（P＝0.000）,与对照组〔（252.91±129.76） pg/mL〕比较,MS组ACTH〔（158.66±92.94） pg/mL〕表达下降（P＝0.024）。不同性别之间上述指标比较差异无统计学意义（均 P＞0.05）。EDSS评分＞4.5组〔（75.74±36.69） pg/mL ,（159.37±27.99） pg/mL〕较EDSS≤4.5组〔（175.07±92.97） pg/mL ,（217.11±65.34） pg/mL〕患者血清ACTH、CRH水平显著降低（P＝0.001,P＝0.032）。非RRMS组患者血清 ACTH、CRH 水平〔（101.62±57.02） pg/mL ,（174.89±52.48） pg/mL〕与RRMS组〔（172.68±96.11） pg/mL ,（215.61±64.89） pg/mL〕比较均显著下降（P＝0.008,P＝0.032）。结论MS 患者存在HPAA 的功能紊乱。     

蜘蛛香提取物的抗焦虑作用：可通过调节下丘脑-垂体-肾上腺轴实现？

摘 要： 目的：观察蜘蛛香提取物对焦虑模型大鼠下丘脑-垂体-肾上腺轴（HPA轴）功能的影响。方法：采用高架十字谜宫大鼠焦虑模型,用蜘蛛香乙醇提取物进行抗焦虑治疗,观察蜘蛛香提取物对焦虑大鼠血液β-内腓肽（β-EP）、皮质酮（CS）的影响;采用基因芯片对不同组别大鼠基因进行表达谱检测,从中筛选与HPA轴相关的差异表达基因。结果：模型对照组大鼠血液β-EP、CS含量明显高于正常组,各用药组的β-EP、CS含量皆有不同程度的减少,其中药物低剂组β-EP含量、药物低剂组和高剂组CS含量与模型对照组比较差异显著(P<0.01、P<0.001、P<0.05)。在基因表达谱检测中,与HPA轴功能相关的促肾上腺皮质激素释放激素（CRH）、神经肽Orexin在不同组别有差异表达,其在模型对照组表达量升高,而在蜘蛛香提取物组其表达水平趋向下降。结论：蜘蛛香提取物对焦虑模型大鼠下丘脑-垂体-肾上腺轴（HPA轴）功能的紊乱有调节作用。     

人参皂甙对应激模型大鼠下丘脑—垂体—肾上腺轴和…

用手术截肢（ａｍｐｕｔａｔｉｏｎ）造成大鼠应激模型，观察下丘脑－垂体－肾上腺轴（ＨＰＡＡ）和脾脏中神经肽Ｙ（ＮＰＹ）阳性细胞数及人参皂甙的调节作用。免疫酶组织化学和免疫荧光检测结果显示：模型大鼠ＨＰＡＡ中ＮＰＹ阳性细胞与正常比较在应激初期（３０ｍｉｎ内）明显减少，随后开始增多，３－６ｈ达高峰，再逐渐至正常水平。脾组织中ＮＰＹ阳性细胞在应激后６０ｍｉｎ多于正常对照，１２ｈ达高峰，２４ｈ接近正常。用人     

急性脑血管病下丘脑-垂体-靶腺轴功能变化的研究

目的　探讨下丘脑 垂体 靶腺轴变化与急性脑血管病 (CVD)的发生、发展的相关性及临床意义。方法　采用放射免疫法检测血浆中甲状腺激素 (T3 、T4) ,促甲状腺激素 (TSH) ,肾上腺皮质激素 (Cor) ,促肾上腺皮质激素 (ACTH) ,性腺激素睾酮 (T) ,雌二醇 (E2 )、促性腺激素 (FSH)的含量。结果　CVD急性期T4、TSH、Cor、ACTH、T、E2 、FSH的含量明显增高 ,T3 的含量下降 (P <0 .0 1)。随着病情的好转各项指标有所恢复。结论　CVD患者下丘脑 垂体 靶腺轴均有改变 ,是可逆的。及时测定观察有关激素的含量变化对诊断疾病 ,预测病情及预后 ,指导治疗有着实际的临床意义。     

急性脑出血下丘脑-垂体-靶腺轴对照研究

目的 :探讨下丘脑 -垂体 -靶腺轴变化与急性脑出血的发生、发展的相关性。方法 :采用放射免疫法检测血浆中甲状腺激素 (T3、 T4 )促甲状腺激素 (TSH) ,肾上腺皮质激素 (Cor) ,促肾上腺皮质激素 (ACTH) ,性腺激素睾酮(T) ,雌二醇 (E2 ) ,促性腺激素 (FSH)的含量。结果 :脑出血急性期 T4 、 TSH、 Cor、 ACTH、 T、 E2、 FSH的含量明显增高 ,T3的含量下降 ,P<0 .0 1。随着病情的好转各项指标有所恢复。结论 :脑出血患者下丘脑 -垂体 -靶腺轴均有改变 ,是可逆的。测定有关激素的含量变化对预测病情及预后 ,指导治疗有临床意义     

抑郁障碍患者下丘脑-垂体-肾上腺轴调节异常对辅助性T细胞17分化发育的影响

目的 探讨抑郁障碍患者的下丘脑-垂体-肾上腺(hypothalamus-pituitary-adrenal,HPA)轴功能异常对辅助性T细胞17(Th17 细胞)分化发育的影响.方法 纳入包括单相抑郁和双相抑郁在内的首次发病未用过药的抑郁发作患者32例及正常对照25名,测定受试者的血浆促肾上腺皮质激素(adrenocorticotrophic hormone, ACTH)、血清皮质醇和细胞因子IL-17的浓度,采用逆转录-聚合酶链反应检测受试者外周血单个核细胞(peripheral blood monouclear cells, PBMC)中糖皮质激素受体(glucocorticoid receptor,GR)和维甲酸相关核孤儿受体γt (retinoid-related orphan receptor gammat,RORγt) mRNA的表达水平.结果 抑郁障碍患者组和正常对照组的PBMC中GR mRNA的表达分别为25.14%和39.56%,患者组显著下降(Z=-2.76,P<0.01);患者组RORγt mRNA的表达、血清IL-17浓度分别为68.70%、83.83 ng/L,而对照组为24.74%、65.60 ng/L,患者组两个指标均显著升高(Z=-3.00,P<0.01;Z=-2.33,P<0.05).患者组中GR mRNA与RORγt mRNA的表达、IL-17浓度均呈负相关(r=-0.70,P<0.01;r=-0.47,P<0.05);未见其余指标间存在相关(P>0.05).结论 HPA轴负反馈调节异常对Th17细胞的分化发育及炎性诱导起重要作用.     

急性脑血管病下丘脑-垂体-肾上腺皮质轴变化的观察

目的　观察急性脑血管病时下丘脑 垂体 肾上腺皮质轴的功能变化。方法　应用放射免疫方法检测急性脑血管病患者肾上腺皮质激素 (Cor) ,促肾上腺皮质激素 (ACTH)的含量。结果　急性脑血管病患者血清ACTH、Cor含量均高于对照组 ,差异有显著性 (P <0 .0 1) ,血清ACTH、Cor含量与脑损伤范围成正比 ,急性脑血管病恢复期血清ACTH、Cor含量明显低于急性期 ,有显著差异 (P <0 .0 1)。结论　急性脑血管病患者血清ACTH、Cor含量均有改变 ,是可逆的。     

糖皮质激素对大鼠下丘脑-垂体-肾上腺轴Ca~(2+)/CaMPKⅡ的影响

目的研究糖皮质激素醋酸可的松对大鼠下丘脑-垂体-肾上腺轴(HPAA)游离钙(Ca2+)及钙调素依赖的蛋白激酶Ⅱ(CaMPKⅡ)的影响。方法用流式细胞仪及钙荧光探针Flou-3/AM来测定细胞中的Ca2+,通过液体闪烁仪测定γ-32P-ATP参入反应底物的摩尔数,用来表示蛋白激酶的活性。结果醋酸可的松组大鼠下丘脑细胞[Ca2+]i荧光强度为129.32±17.74,显著高于对照组60.65±10.64,P<0.05。而醋酸可的松组大鼠下丘脑、肾上腺组织中CaMPKⅡ活性分别为14.07+3.15和3.87+1.47(nmolPi.min-1.mg-1protein),与对照组的7.91+3.2和2.23+0.52(nmolPi.min-1.mg-1protein)相比显著升高,差异有统计学意义,P<0.001。结论糖皮质激素对下丘脑-垂体-肾上腺轴的调控作用与Ca2+、CaMPKⅡ密切相关。     

去卵巢大鼠下丘脑-垂体-卵巢轴的功能代偿机制研究

目的：在细胞和分子水平上，探讨机体因各种原因导致卵巢功能低下时，下丘脑-垂体-卵巢轴(HPOA)功能的自然代偿机制。方法：观察大鼠切除卵巢后1～6个月，下丘脑促性腺激素释放激素(Gonadotmpin releasing hormone，GnRH)及其mRNA表达的改变以及阴道脱落细胞形态和外周血雌二醇(E2)水平的变化。结果：去卵巢后5～6个月时，大鼠阴道涂片出现成熟脱落细胞；4个月时血E2水平明显升高，6个月时几乎稳定在正常水平的一半以上；随去卵巢时间延长，大鼠下丘脑GnRH神经元数目较去卵巢1个月时逐渐增多，至6个月时，升高有显著差异，但仍低于正常组数目；去卵巢1个月大鼠下丘脑组织GnRHmRNA表达明显减少，去卵巢后5个月明显升高，与正常组相比没有显著差异；GnRH棘型神经元的比例在去卵巢4个月时即升高到正常水平。结论：大鼠卵巢功能低下时，机体体内可能存在一种自然代偿作用，使异常的HPOA功能趋于正常化。     

抗精神病药对男性精神分裂症患者垂体-性腺轴的影响

目的：研究氯丙嗪、利培酮、奎硫平及奥氮平对男性精神分裂症患者垂体．性腺轴的影响。方法：88例首发男性精神分裂症患者随机分为氯丙嗪组、利培酮组、奎硫平组及奥氮平组，检测治疗前、治疗4周及8周血清促卵泡素（FSH）、黄体生成素（LH）、催乳素（PRL）、睾酮（T）的水平变化。结果：氯丙嗪组治疗8周后，血清PRL水平显著高于治疗前。利培酮组在治疗4周及8周后PRL水平均显著高于治疗前，治疗8周后T及LH水平显著低于治疗前。奎硫平组在治疗4周及8周后血清PRL、LH、T水平与治疗前比较差异均无显著性。奥氮平组治疗4周后PRL水平显著高于治疗前，治疗8周后即与治疗前差异无显著性。结论：奎硫平对垂体．性腺轴激素水平无明显影响。     

抗精神病药对男性精神分裂症患者垂体-性腺轴的影响

目的:研究氯丙嗪、利培酮、奎硫平及奥氮平对男性精神分裂症患者垂体性腺轴的影响。方法:88例首发男性精神分裂症患者随机分为氯丙嗪组、利培酮组、奎硫平组及奥氮平组,检测治疗前、治疗4周及8周血清促卵泡素(FSH)、黄体生成素(LH)、催乳素(PRL)、睾酮(T)的水平变化。结果:氯丙嗪组治疗8周后,血清PRL水平显著高于治疗前。利培酮组在治疗4周及8周后PRL水平均显著高于治疗前,治疗8周后T及LH水平显著低于治疗前。奎硫平组在治疗4周及8周后血清PRL、LH、T水平与治疗前比较差异均无显著性。奥氮平组治疗4周后PRL水平显著高于治疗前,治疗8周后即与治疗前差异无显著性。结论:奎硫平对垂体性腺轴激素水平无明显影响。     

精神分裂症患者社会功能的神经心理学研究

目的:探讨精神分裂症患者的社会功能。方法:应用神经心理学方法,对精神分裂症患者社会问题解决能力进行研究。结果:精神分裂症患者社会问题解决能力较正常对照明显下降。结论:精神分裂症患者社会问题解决能力的损害可能是社会功能障碍的重要基础。     

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 jatamansi Jones 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 Valeriana jatamansi Jones groups intragastrically injected with 0.3,0.6, and 0.9 g/kg per day Valeriana jatamansi 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 Valeriana jatamansi Jones extract. Expressions of HPA axis-related genes were measured by cDNA microarray.RESULTS: Blood p-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 Valeriana jatamansi Jones extract.CONCLUSION: Valeriana jatamansi Jones extract plays a role in regulating HPA axis function in a rat model of anxiety, and this effect was superior to estazolam.     

首发精神分裂症患者认知功能研究

目的:了解首发精神分裂症患者认知功能损害特点以及治疗对认知功能的影响。方法:对37例符合中国精神障碍分类与诊断标准第3版首发精神分裂症诊断标准的患者于治疗前及治疗8周后采用华文认知能力量表(CCAS)、阳性与阴性症状量表(PANSS)进行评定;同时调查患者的临床特征。结果:精神分裂症患者治疗后CCAS工作记忆(t=3.315,P<0.01)、学习能力(t=4.726,P<0.01)、推理能力(t=4.209,P<0.01)、加工速度(t=6.253,P<0.01)、空间/计算(t=5.111,P<0.01)等认知功能和言语智商(t=3.769,P<0.01)、操作智商(t=3.552,P<0.01)以及总智商(t=3.972,P<0.01)均较治疗前有不同程度提高;治疗前后比较差异均有统计学意义。经Pearson相关分析,治疗前后总智商的差值与PANSS总分及阳性总分差值具有相关性(r分别=0.564、0.756,P<0.05)。结论:首发精神分裂症患者在发病初期就存在认知功能损害;奥氮平等药对精神分裂症的认知损害具有一定改善作用,短时记忆某些成份的改善与精神症状(阳性症状)的好转具有相关性。     

老年期女性脑卒中后抑郁患者下丘脑-垂体-性腺轴功能变化的研究

目的 探讨老年期女性脑卒中后抑郁下丘脑-垂体-性腺轴功能变化。方法 选择102例老年期女性病程4周内脑卒中患者按中国精神疾病分类方案与诊断标准第二版（CCMD-2-R）、DSM—IV诊断标准确定脑卒中后抑郁（PSD）,分为非PSD组、PSD组,并设健康老年对照组,均于1周、2周、4周采用放射免疫法测定血清卵泡刺激素（FSH）、黄体生成素（LH）、雌二醇（E2）、孕酮（P）,HAMD、抑郁自评量表（SDS）评分均在病程1周、2周、4周、与性激素测定采血同日进行。结果 PSD组FSH、LH在1周、2周、4周呈逐渐上升;PSD组与对照组FSH、LH在1周、2周、4周比较有极显著性差异（P〈0．01）;PSD组与对照组E2、P比较均无显著性差异（P〉0．05）。PSD组FSH、LH动态变化与HAMD、SDS评分呈正相关（P〈0．05）,E2、P与HAMD、SDS评分无相关。结论 PSD患者存在下丘脑-垂体-性腺轴功能异常;动态测定血清性激素变化可及早判别PSD。     

Hypothalamus pituitary adrenal axis and autonomic activity during stress in delinquent male adolescents and controls

OBJECTIVE: Patterns of low autonomic arousal have consistently been related to delinquency and disruptive behavior disorders (DBD) in children and adolescents. Findings on another stress regulating mechanism, the hypothalamic pituitary adrenal (HPA) axis, have been inconsistent, which may partly be due to not considering specific stress reactivity measures. Therefore, the aim of the present study was to investigate the relationship between disruptive behavior in male adolescents and their HPA and autonomic reactivity to a standard public speaking task (PST). METHOD: Responsivity to the PST of cortisol, heart rate (HR), skin conductance level (SCL) and self-reported negative feelings was measured, and compared between 12and14-year-old boys who attended a delinquency diversion program (DP), with and without DBD (DP+, n=22 and DP-, n=49, resectively), and matched normal controls (NC, n=30). DBD diagnoses were based on a structured psychiatric interview. RESULTS: The DP+ group, but not the DP- group, showed a significantly decreased cortisol and HR response during the PST as compared with the NC group. No significant effects were found for SCL. All subjects connoted the task negatively. CONCLUSIONS: The results indicate that low cortisol and HR responsivity to stress may be a neurobiological marker for delinquent boys with DBD, but not for those without DBD. Directions for future research and clinical implications are discussed.     

Hypothalamic pituitary adrenal axis and immune responses to endotoxin in rats with chronic adjuvant-induced arthritis

We investigated the effect of immune challenge with LPS in both control rats and rats with adjuvant-induced arthritis (AA). Fourteen day-AA rats showed the expected activation of the hypothalamic-pituitary adrenal axis associated with increases in vasopressin mRNA and paradoxical decreases in corticotropin-releasing hormone (CRH) mRNA in parvocellular neurons of the hypothalamic paraventricular nucleus (PVN). However, following LPS there was an increase in both CRH and vasopressin mRNA in the PVN. Neither control rats nor rats with AA had measurable plasma levels of IL-6, but plasma levels of IL-1beta were 2.7-fold higher in AA animals. Following LPS injection both IL-1beta and IL-6 increased more markedly in AA than in control rats. Neither controls nor AA rats expressed IL-1beta or IL-6 mRNA in the brain. However, following LPS these were induced in the subfornical organ, choroid plexus, and median eminence of both groups of animals. The areas expressing IL-1b mRNA were larger in the AA animals and exhibited a punctate pattern throughout the brain parenchyma and PVN. These data reveal an increased peripheral and central immunological response to LPS during the chronic inflammatory process of AA, providing a mechanism through which inflammatory disease can influence the response to a novel immunological challenge.