慢性社会应激对大鼠神经内分泌及行为的影响

社会应激 (socialstress,SS)或心理社会应激是由诸多机体不适应的社会环境因素 (如复杂的人际关系、拥挤的环境、经济压力等 )引起的应激 ,它包括心理性应激反应以及伴有神经内分泌改变的生理性或病理性应激反应。研究表明 ,持续的慢性社会应激 (CSS)会直接或间接地导致一系列心身疾病。在特殊环境条件下 (例如极地科考 ,航天等 ) ,CSS可能引发的心理障碍也是一个备受关注的问题。CSS对机体的负面影响的生理机制尚不完全清楚。作为探讨CSS的可能心理生理机理 ,本文参考了有关的方法[1 ] 并加以改进后 ,观察了CSS所引起的内分泌系统以…     

神经内分泌激素与自身免疫性疾病

下丘脑垂体通过各自相应的轴所释放产生的神经内分泌激素,通过与免疫细胞表面相应的受体结合而影响机体免疫功能。近年来研究认为,多种自身免疫性疾病的发生、发展与神经内分泌激素失调存在一定的相关性。     

树突状细胞与相关激素的基础研究

内分泌系统和免疫系统之间的联系是近十几年来的研究热点。研究显示，淋巴细胞膜表面有多种神经递质受体及激素受体，提示神经内分泌系统通过其递质或激素和淋巴细胞膜表面受体结合，介导免疫系统的调节。另外，神经内分泌细胞膜上有免疫反应产物如白细胞介素（IL-1、IL-2、IL-3、IL-6等）、胸腺肽等细胞因子的受体，免疫系统也可通过细胞因子对神经内分泌系统的功能发生影响，甚至产生免疫反应性激素，如ACTH、TSH、HCG、生长激素等．     

5-HT及其受体与神经免疫内分泌网络

神经免疫内分泌学是介于神经内分泌学和免疫学之间的一门边缘学科，学科内部各系统之间存在着双向联系，借助于系统之间共有的信息分子，如神经递质、激素和细胞因子及其受体的相互作用进行信息交流并相互影响而形成一个功能整体。5-羟色胺(5-hydroxytryptamine，5-HT）是一种重要的神经递质，近十几年来，人们发现它对免疫系统也有一定的作用。     

调肝方药对慢性束缚应激大鼠神经内分泌免疫功能的影响

七情致病理论及其防治是中医病因病机学中的一个重要内容,但目前相关研究较少,现代医学中的心理应激理论与中医七情学说在认识上存在着许多共同点,从应激角度出发,结合中医"怒伤肝"的理论,以束缚制动作为应激原,复制慢性激怒应激反应大鼠模型,并探讨调肝方药(TGFY)对应激大鼠神经内分泌免疫功能的影响。1 材料与方法1.1 主要试剂 细胞培养液RPMI-1640(Gibco产品),刀豆素A(ConA,Sigma产品),3H-TdR(中国科学院原子能研究所产品),莨菪葶(9．61μg,Sigma产品),辣根过氧化物酶(HRP,10μg,Sigma产品),十四酰佛波乙酸酯(PMA,100ng,Sigma产品)。125I-CRH、125I-ACTH、125I-CORT放免检测药盒(美国DPC产品)。1.2 大鼠应激模型制作及分组处理 雄性Wistar大鼠,体重250～300 g,分为正常对照组10只(正常饮食,不给任何刺激);慢性束缚应激组1O只(给予束缚刺激,正常饮食,不给中药治疗);调肝方药组10只(给予束缚刺激的同时灌胃调肝方药)。慢性束缚应激反应大鼠模型的制作取雄性Wistar大鼠20只,体重250～300 g,每2只一笼,每日给予黑暗和光照各12 h,20～22℃,同时给予每日1次成对双后肢的立式束缚,以引起明显的激怒应激反应(粗叫、站立对峙、扭打嘶咬),首次30min,以后隔日增加10min,共2 w。普通饲料,自由饮水。于实验第13天和第14天在动物清醒、安静状态下断头处死取材。1.3 药物组成剂量及给药方法 所用中药均由本校第一附属医院药房提供的纯正药材。调肝方药组成及剂量：柴胡15g、白芍15 g,香附10 g,山萸肉15 g,郁金10 g,枳壳10g。将上述药物制成100％水煎剂,每毫升含生药1 g,给予大鼠1 ml／100 g体重灌胃,每日2次,共2 w。对照组及应激组灌服等量生理盐水。     

肺及胃肠道神经内分泌肿瘤相关基因研究进展

目前对肺及胃肠道神经内分泌肿瘤（NETs）相关基因研究较多,LOH、比较基因组杂交(CGH)、微卫星不稳定(MSI)、甲基化特异性PCR(MSP)等方法都是目前研究肿瘤遗传学采用的热门技术,这些方法已证实了MEN1基因的杂合性缺失（LOH）、DNA拷贝数丢失、启动子甲基化。消化道NETs 11q、18q的DNA拷贝数的丢失;小细胞肺癌（SCLC）的微卫星不稳定（MSI）和SCLC在RARβ, CDH1, RASSF1A基因启动子区的高频甲基化也已存在较肯定的实验结果。本文对肺及胃肠道神经内分泌肿瘤相关基因的研究作一概述,包括研究方法、基因改变的分子机制和基因组不稳定性。     

跳伞应激对空降兵新兵神经内分泌的影响

近年来神经内分泌研究成为预防医学和军事医学的优先发展领域和研究前沿。其研究对提高空降兵部队的心理健康水平和紧急状态下的应对能力 ,最大限度减低非战斗减员的发生率具有重要意义。国外跳伞人员 (非伞兵 )神经内分泌学研究偏重于与应激有关的下丘脑—垂体—肾上腺轴系统 (皮质醇、ＡＣＴＨ等 )及内源性阿片肽的研究[1-6] ,对其它系统及神经肽的变化研究甚少。本研究就空降兵新兵群体在跳伞应激状态下精氨酸血管加压素 (ＡＶＰ)、神经肽Ｙ(ＮＰＹ)、降钙素基因相关肽 (ＣＧＲＰ)、神经降压素 (ＮＴ)、血管活性肠肽 (ＶＩＰ)的变化规律…     

正常男性血清生殖内分泌激素与睾丸、精液的相关研究

激素是协调机体不同代谢作用的化学信使。生殖内分泌激素与男性的睾丸发育、精子发生及性功能密切相关[1] 。下丘脑分泌促性腺激素释放激素 (GnRH)作用于垂体前叶分泌促性腺激素 ,包括促卵泡成熟激素 (FSH)、黄体生成素 (LH)和垂体泌乳素 (PRL)。FSH作用于睾丸支持细胞产生抑制素B ,参与FSH的反馈调节 ,LH则作用于睾丸间质细胞产生睾酮(T)。曲细精管和男性附属性腺的功能是受雄激素调节 ,这些激素的分泌同时受多种因素影响。为了探讨正常男性血清中生殖内分泌激素的水平及其与相关因素的关系 ,我们从 2 0 0 0年 1～ 12月对 5 2 3名…     

胃肠激素对胃肠动力的影响

胃肠激素与其他成分如神经递质、细胞因子等互相作用、相互调节,维持机体正常生理功能。胃肠激素与胃肠运动密切相关,同时也受神经内分泌免疫网络调控,由此本文综述其在神经内分泌网络中的特殊作用及其对胃肠动力方面的影响。     

光照应激对SD大鼠胃促性腺激素释放激素受体表达的影响

目的 观察光照应激状态下SD大鼠胃内促性腺激素释放激素受体（GnRHR）的表达变化。 方法 建立SD大鼠光照应激模型(共64只,实验组与对照组各32只),24h持续光照,分别取光照1d、2d、3d、4d、1周、2周、3周、4周和相应对照组大鼠的胃,采用免疫组织化学、Western blotting和实时PCR法检测GnRHR在各时间段大鼠胃黏膜中的定位及蛋白和mRNA的表达变化。 结果 GnRHR阳性细胞广泛分布于大鼠胃底腺壁细胞中,在对照组和实验组中的定位无差异。实验组大鼠的GnRHR蛋白表达水平高于其相应的对照组。持续光照1～4周后,实验组与其对照组相比差异显著（P<0.05）;当持续光照2周时,GnRHR的表达至最高水平,与其对照组相比,差异极显著（P<0.01）。实验组大鼠胃GnRHR mRNA表达水平高于对照组,持续光照3～4周后,实验组大鼠胃GnRHR mRNA表达水平显著增加（P<0.05）。 结论 光照应激可以影响消化道内GnRHR的表达,提示GnRH通过其受体介导,对消化功能具有潜在的生理调节功能。GnRH除参与消化道正常生理功能外,可能还是一种参与应激反应的激素。     

Differential expression of somatostatin receptors 1-5 in neuroendocrine carcinoma of the lung

The majority of neuroendocrine carcinomas (NECs) express somatostatin (SST) receptors (SSTRs). However, the expression of all 5 SSTR subtypes in pulmonary NECs has not been reported. We performed immunohistochemical analysis of all 5 SSTR subtypes (including the SSTR2A and 2B isoforms). In typical carcinoids, immunoexpression of SSTR 1, 2A, 2B, 3, 4, and 5 was observed in 47/56 (79.7%), 57/58 (96.6%), 39/59 (66.1%), 28/57 (49.1%), 3/58 (5.2%), and 0/57 cases, respectively. In atypical carcinoids, immunoexpression of SSTR 1, 2A, 2B, 3, 4, and 5 was observed in 7/9 (77.8%), 7/9 (77.8%), 7/9 (77.8%), 3/9 (33.3%), 0/9, and 0/9 cases, respectively. In large cell NECs, immunoexpression of SSTR types 1, 2A, 2B, 3, 4, and 5 was observed in 12/20 (60%), 12/20 (60%), 6/20 (30%), 8/20 (40%), 0/20, and 3/20 (15%) cases, respectively. In small-cell carcinomas, immunoexpression of SSTR types 1, 2A, 2B, 3, 4, and 5 was observed in 16/54 (27.6%), 40/56 (69%), 14/56 (24.1%), 9/56 (15.5%), 0/58, and 2/55 (3.4%) cases, respectively. Except for SSTR5, all SSTRs showed a tendency toward decreased expression in well- to poorly differentiated NECs. We believe that these findings indicate important implications for the future of SST analog therapy.     

固真方对环磷酰胺大鼠神经内分泌及免疫系统部分功能的调节作用

腹腔注射环磷酰胺(Cy)以后大鼠下丘脑单胺类神经递质及其代谢产物发生紊乱;血浆β-EP 浓度持续性增高;下丘脑-垂体-性腺轴功能及脾淋巴细胞免疫功能低下.固真方能纠正下丘脑单胺类神经递质及其代谢产物的紊乱,降低血浆β-EP 浓度,调节下丘脑-垂体-性腺轴功能.四君子汤对神经内分泌系统功能紊乱的调节作用不及同真方广泛。     

The influence of fitness on neuroendocrine responses to exhaustive treadmill exercise

Summary Neuroendocrine and sympathoadrenal responses to exhaustive graded treadmill exercise were examined in 17 male subjects of varying degrees of fitness. The mean duration of exercise to exhaustion was 15.2±0.7 (±SE) min. Exercise duration was inversely correlated with baseline heart rate (P<0.05). Compared to standing baseline values, mean plasma norepinephrine and epinephrine levels increased 339% and 301%, respectively, in an integrated 2-min blood sample collected immediately after completion of exercise. Mean adrenocorticotrophic hormone (ACTH),β-endorphin (β-EP),β-lipotropin (β-LPH), and prolactin levels increased 282%, 720%, 372%, and 211%, respectively, in an integrated 4-min blood sample beginning 2 min after completion of exercise. Cortisol levels increased 183% in the sample collected 17–21 min after exercise. The magnitude of these neuroendocrine responses to exercise was similar among individuals at the same relative intensity of exhaustive exercise, regardless of the duration of exercise. The exercise-induced increases of the pro-opiomelanocortin (POMC)-derived peptides, ACTH,β-EP, andβ-LPH, were highly correlated with each other (P values <0.001), and were correlated with prolactin increases, (P values <0.05). During a 20-min recovery period after exercise, changes in heart rate, ACTH, andβ-LPH levels were correlated with duration of exercise, (P<0.01,P<0.03, andP<0.03, respectively). Assuming that the duration of exercise reflects fitness, these data suggest that the pattern of POMC-derived peptide responses during recovery from exhaustive exercise is dependent on fitness. The views of the author(s) do not purport to reflect the position of the Department of the Army or the Department of Defense, (para 4-3, AR 360-5). Human subjects participated in these studies after giving their free and informed consent. Investigators adhered to AR 70-25     

Effects of N-methyl-D-aspartate-induced amygdala lesion in rats submitted to the elevated T-maze test of anxiety

The elevated T-maze (ETM) has been used to generate two defensive behaviors in the same rat, inhibitory avoidance and one-way escape, which have been related to generalized anxiety and panic, respectively. In the present study, we investigate the role of the amygdala on the modulation of these two behaviors. Male Wistar rats were tested in the ETM test 2, 7, or 14 days after bilateral N-methyl-D-aspartate (NMDA)-induced lesion of the amygdala. The animals were also tested in an open field for evaluation of motor performance. The results showed that animals tested 7 days after NMDA injection had impairment in the acquisition of inhibitory avoidance, indicating an anxiolytic effect. Lesion of the amygdala did not change one-way escape in any of the tested groups. These results provide further evidence for the involvement of the amygdala in the modulation of defensive behaviors that have been associated to generalized anxiety.     

Stress and pregnancy loss: role of immune mediators, hormones and neurotransmitters

This review highlights recent studies investigating the impact of stress on pregnancy health or loss. Spontaneous abortion is the most common adverse pregnancy outcome, and stress has been suggested to be abortogenic in mice and humans. A wealth of information has been published on the effect of stress on the nervous, endocrine and immune systems during the past two decades. Stress- and/or pregnancy-related hormones (corticotropin releasing hormone, adrenocorticotropin, prolactin, and progesterone) might interact with peripheral and local immuncompetent cells, such as certain T cell subsets, mast cells or NK cells, and result in changes of cytokine production. Since a well-balanced interaction of nervous, endocrine and immune system is crucial for the maintenance of successful pregnancy, putative mechanisms and recent observations on stress-triggered pregnancy failure have been reviewed.     

Resocialisation of isolation-reared rats does not alter their anxiogenic profile on the elevated X-maze model of anxiety

Rats were reared from weaning either in isolation or in social groups for 30 days and their behaviour on the elevated X-maze was studied. Isolation-reared rats displayed an anxiogenic profile on the X-maze compared to socially reared controls. Resocialisation of isolation-reared rats for a further 30 days did not reverse this anxiogenic profile, and isolation of the socially reared rats for 30 days did not produce an anxiogenic behavioural profile, indicating that the differences observed may be a result of a permanent developmental change. The locomotor hyperactivity induced by isolation was specific to the rearing conditions. It remains to be determined what neurochemical events are involved in the sustained effects of rearing in isolation.     

The effect of experience and hormones on the initial receptivity in female and male rats

Factors investigated were those influencing the increase in receptivity recorded in spayed females and neonatally androgenized males following successive injections of estradiol benzoate and progesterone. After being first submitted to the standard testing regimen, consisting of both hormone injections and mating with vigorous males in a testing arena, females exposed to hormones alone or to the testing situation alone or to the standard regimen manifest the same increase in receptivity as measured in later tests. Equivalence between hormones and experience with vigorous males in elevating receptivity tendency is absent in females not having the standard mating tests first and in neonatally castrated males. In both instances, experience with vigorous males in the testing arena does not markedly raise receptivity propensity. Hormone injections alone increase receptivity tendency in females, but to a lesser extent than when interaction with males is permitted.     

Aging effects on elevated plus maze behavior in spontaneously hypertensive, Wistar-Kyoto and Sprague-Dawley male and female rats

Male and female spontaneously hypertensive (SHR), Wistar-Kyoto (WKY), and Sprague-Dawley (SD) rats were assessed at one of two ages (postnatal day 74 or 346) for open field locomotor activity and anxiety-related behavior in the elevated plus maze (EPM). In general, the SHR displayed the least anxiety-related behavior, an effect that was magnified with age. At 11 months of age, the SHR more frequently entered and remained longer in the open arms than either the SD or the WKY strains. EPM behavior of the WKY strain was much less affected by age than that of the SD strain which displayed increased anxiety-related behavior with age. At the younger age, the typical sex effects were apparent; specifically, females exhibited a shorter duration in the closed arms. While the SHR were the most active strain in the EPM at both ages, they were more active in the open field only at the older age. In general, age-related changes in open field activity mirrored those of the EPM. These results provide a more comprehensive illustration of aging-related behavioral changes in male and female SHR, WKY and SD rats.     

Claudin-5和CD99在胰腺实性-假乳头状肿瘤和神经内分泌肿瘤中的表达及其意义

目的 研究内皮细胞间紧密连接蛋白Claudin-5和细胞间黏附分子CD99在鉴别胰腺实性-假乳头状瘤(SPN)与胰腺神经内分泌性肿瘤(P-NET)中的意义.方法 应用免疫组织化学MaxVision法检测于2003至2012年收集的37例SPN、21例P-NET组织中Claudin-5和CD99的表达情况.结果 37例SPN,Claudin-5在细胞膜表达,阳性率为100％;21例P-NET,Claudin-5均不表达;两者之间差异有统计学意义(P＜0.01).CD99在SPN和P-NET中的表达模式不同,前者呈核旁点状聚集,后者在细胞膜表达,其表达率分别为91.9％(34/37)和61.9％(13/21);两者之间差异有统计学意义(P＜0.01).Claudin-5和CD99在SPN中的表达呈显著正相关(r=0.421,P=0.001).结论 对于大体和镜下特征与P-NET相似的SPN病例,仅依靠形态学诊断十分困难.免疫组织化学联合检测Claudin-5和CD99则对鉴别诊断有重要意义.     

The effect of stress on the expression of the amyloid precursor protein in rat brain

The abnormal processing of the amyloid precursor protein (APP) is a pivotal event in the development of the unique pathology that defines Alzheimer's disease (AD). Stress, and the associated increase in corticosteroids, appear to accelerate brain ageing and may increase vulnerability to Alzheimer's disease via altered APP processing. In this study, rats were repeatedly exposed to an unavoidable stressor, an open elevated platform. Previous studies in this laboratory have shown that a single exposure produces a marked increase in plasma corticosterone levels but animals develop tolerance to this effect between 10 and 20 daily sessions. Twenty-four hours after stress, there was an increase in the ratio of the deglycosylated form of APP in the particulate fraction of the brain, which subsequently habituated after 20 days. The levels of soluble APP (APPs) tended to be lower in the stress groups compared to controls except for a significant increase in the hippocampus after 20 days of platform exposure. Since APPs is reported to have neurotrophic properties, this increased release may represent a neuroprotective response to repeated stress. It is possible that the ability to mount this response decreases with age thus increasing the vulnerability to stress-induced AD-related pathology.