脑创伤后血清皮质醇测定的临床价值

皮质醇(cortisol)是糖皮质激素(glucocorticoids,GCs)的主要激素,是机体对外界刺激产生反应的重要激素,是维持内环境稳态所必需的因子。内源性皮质醇的合成与分泌主要由下丘脑-垂体-肾上腺(hypothalamic - pituitary - adrenal,HPA)轴所调节。不同程度不同类型脑创伤可观察到不同的内源性皮质醇水平变化。严重应激性脑创伤状态下,HPA轴的调节机制可能受到损害,从而导致肾上腺皮质分泌功能的异常。皮质醇作为重要的"应激"激素,测定其外周血液浓度可帮助评价机体脑创伤后的内分泌变化,指导糖皮质激素的应用及估计预后。     

糖皮质激素受体在抑郁症病理机制中的地位

抑郁症是一种反复发作的情绪性障碍，其病理机制尚未彻底阐明。传统认为抑郁症与脑内单胺能神经递质系统失调有关，但抗抑郁药引起单胺递质的快速变化与产生临床疗效需要数周之间的矛盾，难以用此做出合理解释。进而研究者把目光投到了单胺类以外的递质和受体，为研发新型抗抑郁药提供新的作用靶点。本文将就糖皮质激素受体（glucocorticoid receptor，GR）在抑郁症中的作用机制及临床应用方面进行综述。     

自由基、糖皮质激素与脑损伤

越来越多的研究结果表明,自由基在多种脑外科疾病发展过程中都起着重要的作用,重新认识了糖皮质激素在脑损伤中的治疗价值。本文就自由基在脑损伤中的作用、脑损伤后病理性自由基反应机理、糖皮质激素在脑损伤中的作用以及糖皮质激素抗脑水肿的作用机制进行了综述     

糖皮质激素与免疫功能的关系及在运动免疫学中的作用★

学术背景：长期以来，糖皮质激素作为一种免疫抑制剂，一直被认为对免疫功能只有抑制作用；然而运动免疫学中的许多研究结果却难以用糖皮质激素的抑制理论作解释。 目的：分析糖皮质激素与免疫功能的关系及其在运动免疫学中的作用。 检索策略：应用计算机检索Medline1970-01/2007-12有关糖皮质激素与免疫功能及运动免疫学关系方面的文章，检索词为“glucocorticoid(GC)，immunity，exercise”，限定语言种类为English。同时检索中国期刊网1990-01/2007-12有关糖皮质激素与免疫功能以及运动免疫学关系方面的文章，检索词为“糖皮质激素，免疫，运动”，并限定语言种类为中文。同时查阅相关的教材书。对资料进行初审，选择有关糖皮质激素与免疫功能关系的文献，特别是糖皮质激素提高免疫功能，以及运动与上呼吸道疾病关系的文献。排除综述类及重复文献。共检索到75篇文献，30篇文献符合纳入标准，排除45篇；同时参考了3本教材中的相关内容。 文献评价：纳入的33篇文献中有关糖皮质激素调节免疫功能经典理论的文献12篇，有关糖皮质激素调节免疫功能新观点的文献14篇，有关应用糖皮质激素调节免疫功能的新观点分析运动免疫学中两个基本理论的文献7篇。 资料综合：近年来发现糖皮质激素与免疫功能的关系比较复杂，在一定的条件下，它对免疫功能具有加强作用。在运动与健康的关系中，现在比较一致的观点是，中等强度的运动有益于身体健康，而在大强度的运动后运动员抵抗力下降，更易患急性上呼吸道疾病，上呼吸道疾病主要是由病毒引起的一种疾病，运用糖皮质激素对免疫功能的作用可以比较合理的解释运动中有机体产生这些变化的原因。 结论：低浓度的糖皮质激素对免疫功能具有增强作用，高浓度的糖皮质激素抑制细胞免疫增强体液免疫；大强度的训练后运动员抵抗力下降，更易患急性上呼吸道疾病是由于大强度的训练后运动员细胞免疫功能下降，体液免疫增强的结果。     

细胞凋亡与实验性变态反应性脑脊髓炎

凋亡是细胞的一种主动死亡形式,与神经系统自身免疫性疾病的发生、发展和转归密切相关。本文对凋亡的形态、生化特征及其基因调控、T细胞的凋亡机制和糖皮质激素的影响以及凋亡在实验性变态反应性脑脊髓炎发病中的作用作一综述。     

应激抑制神经再生：糖皮质激素及其受体参与的作用？

背景及目的—应激抑制神经再生的效应众所周知,但确切的机制仍不清楚,由于糖皮质激素受体在脑内广泛分布,应激释放的糖皮质激素主要通过与糖皮质激素受体(glucocorticoid receptor,GR)结合而发挥系列生物学效应,因此研究脑缺血后神经再生的激活、增殖、迁移及分布与脑内GR变化间的联系,或将揭示新生神经细胞受糖皮质激素水平调控的可能机制。方法—选取9-10周龄成年wistar大鼠,使用线栓法致其大脑中动脉闭塞0.5小时,脑缺血损伤诱导成功后重复腹膜下注射细胞增殖特异性标记5-溴脱氧尿苷（5-bromodeoxyuridine,BrdU）。灌流大鼠前取其心血制成血清标本用于皮质酮定量分析。使用ABC免疫组织化学方法,鼠脑切片行GR以及新生神经细胞的双标免疫染色。结果—脑缺血后大鼠应激激素皮质酮水平逐渐升高,术后第3周时皮质酮水平达到最高峰,其后逐步回落;GR+细胞数量术后逐渐减少,而血管内皮增生及神经生发等脑缺血后再生修复改变亦呈动态变化,BrdU及Nestin﹢细胞数量在术后第1、2周显著增加,DCX﹢细胞较多,由海马至皮层的迁移现象明显;至第3周起BrdU及Nestin﹢细胞数量明显减少且仅散布在室管膜周边,第4周时BrdU﹢细胞仍少见,仅缺血侧海马及纹状体DCX反应较明显。假手术组大鼠应激激素皮质酮水平术后即明显升高,其后呈现出逐渐降低的趋势,术后第3周,其水平逐渐稳定。术后第1、2周,各脑区GR﹢细胞正常分布,主要神经生发区可见一定数量的BrdU+、Nestin+及DCX+细胞存在;第3周时各脑区包括海马GR﹢细胞数量减少,仅皮层可见个别DCX﹢细胞,BrdU﹢细胞极少。结论—脑缺血后大鼠应激激素皮质酮水平逐渐升高,GR+细胞数量逐渐减少,而血管内皮增生及神经生发等脑缺血后再生修复改变与其相联系而呈动态变化,表现为皮质酮水平升高,GR+细胞数量减少,神经再生受抑制。假手术对照组大鼠并无血管内皮增生等损伤后改变,而皮质酮水平虽然快速升高,但GR数量及分布似乎并未受到影响,至少没有受到立即的直接影响,而主要神经生发区存在一定数量的神经干细胞及其迁移现象,这提示在正常状况下,或许存在某些机制能调节或者抑制皮质酮水平对糖皮质激素受体及神经再生的直接影响。     

Melatonin的脑保护机制研究进展

Melatonin(MT)是松果体分泌的一种神经内分泌激素,它不仅参与生物周期性节律、神经-内分泌-免疫调节、镇静、催眠等,而且在脑缺血、Alzheimer病、癫痫、失眠等多种脑部疾病中具有保护作用。目前发现清除自由基、调节中枢神经递质、调节细胞膜离子通透性、抑制神经元凋亡等是MT脑保护的主要机制。     

糖皮质激素对颅脑损伤的作用

糖皮质激素具有抗炎和减轻水肿的作用,用于治疗颅脑损伤已有20余年,主要的作用机制不完全清楚,而且目前临床应用有很大争议。本文综述了糖皮质激素在颅脑损伤早期的抗炎和抑制脂质氧化作用,以及糖皮质激素治疗过程中引起神经元丢失和抑制神经营养因子、生长因子等影响神经元生存的副作用,供临床应用和进一步研究提供参考。     

糖皮质激素对大鼠大脑皮层突触体高亲和摄取L—谷氨酸的快速,非基因组效应

本研究采用大鼠大脑皮层突触体，观察糖皮质激素（ＧＣ）对于Ｎａ＋依赖高亲和摄取３Ｈ－Ｌ谷氨酸（孵育４ｍｉｎ）的影响。发现ＧＣ包括皮质酮硫酸盐（Ｂ－ＳＯ４）、氢化可的松琥珀酸盐（Ｆ－ｓｕｃ）、地塞米松磷酸盐（ＤＥＸ－ＰＯ４）及皮质酮（Ｂ）均促进突触体摄取谷氨酸，且呈一定浓度依赖性。Ｂ－ＳＯ４１０－５ｍｏｌ／Ｌ时，谷氨酸摄取较对照组增加２５．６％，Ｂ－ＳＯ４、Ｆ－Ｓｕｃ及Ｂ最低有效剂量均为１０－７ｍｏｌ／Ｌ，ＤＥＸ－ＰＯ４最低有效剂量为１０－６ｍｏｌ／Ｌ。孵育２ｍｉｎ后即见Ｂ－ＳＯ４（１０－６ｍｏｌ／Ｌ）促进突触体摄取谷氨酸，孵育４ｍｉｎ后Ｂ－ＳＯ４的作用达高峰。１０－６ｍｏｌ／Ｌ睾酮及孕酮也有促进摄取谷氨酸的作用，而去氧皮质酮及１７β－雌二醇硫酸盐对突触体摄取谷氨酸没有显著影响，ＧＣ的作用有一定甾体特异性。ＧＣ胞内受体阻断剂ＲＵ４８６本身对谷氨酸摄取没有影响，但可部份阻断Ｂ的促进作用。由于已从神经元上离断下来的突触体不再受基因组机制影响，本实验中ＧＣ快速促进突触体摄取谷氨酸是非基因组机制介导的，其详细机制及潜在生理意义有待进一步探讨。     

抑郁症的生化和解剖基础

既往 ,我们对抑郁症的生化改变做过不少描述 ,但很少涉及这些改变的位置。现在 ,随着脑影像学的发展 ,我们有条件研究抑郁症脑异常的部位。所以 ,本文力图将生化和解剖结合起来描述。1　抑郁症的生化机制1.1　童年不良遭遇与抑郁素质　童年长期不良遭遇能过于持久地激动下丘脑 -垂体 -肾上腺 (ＨＰＡ)轴。在正常情况下 ,升高的皮质醇通过激动海马Ⅱ型糖皮质激素受体而抑制ＨＰＡ轴。可是 ,当Ⅱ型糖皮质激素受体过度激动时 ,能破坏海马神经元 ,使ＨＰＡ轴脱抑制性兴奋 ,皮质醇升高 ,后者诱导肝脏色氨酸吡咯化酶 ,降解血液中的色氨酸 ,色氨酸…     

Mechanisms of the suppression of the nociceptive reflex of the opening of the mouth during stimulation of the structures of the limbic brain

The comparative effectiveness of the inhibitory influence of tetanic stimulation of hypothalamus, amygdala and limbic cortex on EMG-response of m. digastricus evoked by electrical stimulation of tooth pulp nociceptive afferents was studied in cats anesthetized with a mixture of chloralose and nembutal. It was found that inhibition of the EMG-component of the jaw-opening reflex is most pronounced in case of stimulation of medial and lateral region of the hypothalamus, the inhibitory effect of central and medial nuclei of the amygdala is less pronounced and the effect of the limbic cortex is the weakest. It was shown that the mechanism of the antinociceptive effect of tetanic stimulation of the hypothalamus is not related to the concomitant increase of the blood pressure. After stabilization of the blood pressure the suppressive effect of the hypothalamus remains without changes, that points out to a direct, primary, not baro-afferent mechanism of the inhibition of the activity of nociceptive neurons of the trigeminal sensory nuclei. Noradrenaline, injected intravenously, induced a large increase of the blood pressure accompanied by a pronounced inhibition of the pain reflex. Angiotensin causes the same degree of blood pressure elevation without changes in the amplitude of the EMG-response of the pain reflex. Hypothalamic and noradrenergic mechanisms for control of pain sensitivity are discussed.     

药物治疗与合并认知行为治疗对强迫症疗效的比较

目的探讨认知行为心理治疗(CBT)在强迫症(OCD)患者各亚型治疗中的有效性和规律性。方法本研究为临床对照研究。符合入组标准的强迫症患者按患者自愿原则分为两组,治疗观察3、6、12个月。疗效评定分别运用Yale-Brown强迫量表,自拟的自评好转程度量表和临床疗效评定。结果认知行为心理治疗合并药物治疗组31例,临床有效率70.9%,其中治愈率1.8%。单纯药物治疗组24例,临床有效率33.3%。Yale-Brown强迫量表和自评量表得分在6个月和12个月两组有显著差异(P<0.05)。其中强迫症亚型(怕脏型、反复检查型和反复担心型)的疗效比较,怕脏型在治疗3个月末两组间自评量表评分有显著性差异(P<0.05);反复担心型在治疗6个月末两组间Yale-Brown强迫量表总分有显著性差异(P<0.05);反复检查型两组间无统计学差异。结论认知行为心理治疗合并药物治疗强迫症的疗效明显优于单纯药物治疗。强迫症的亚型在治疗中的有效性次序为:反复担心型>怕脏型>反复检查型。     

Characteristics of the sympathetic innervation of the nictitating membrane and of the vasculature of the nose and tongue of the cat

Summary Vasomotor responses from the nasal mucosa and tongue, and contractions of the nictitating membrane, were recorded on stimulation of the cervical sympathetic or internal carotid nerves.Preganglionic sympathetic nerve fibres which elicited a membrane response possessed a lower threshold than those which evoked nasal vasoconstriction, while the latter displayed a lower threshold than fibres which evoked tongue vasoconstriction. The sympathetic vasodilator fibres to the tongue, whose activity was revealed after-receptor blockade, had a similar threshold to the vasoconstrictor fibres.Membrane contraction, nasal vasoconstriction and occasionally tongue vasoconstriction could be evoked by stimulating the internal carotid nerve. The postganglionic fibres innervating the nasal mucosa had a similar threshold to those of the nictitating membrane, which may indicate that there are small myelinated fibres innervating the mucosa.The preganglionic compound nerve action potential had four major components, S₁–S₄. S₁, S₂ and usually S₃ fibres were associated with membrane contraction; S₂, S₃ and sometimes S₁ fibres were associated with nasal vasoconstriction; and S₃, usually S₂ and occasionally S₁ fibres were associated with vasoconstriction in the tongue. It is concluded that each of these three groups of nerve fibres, but not S₄ fibres, may include fibres associated functionally with the three effectors.There was a considerable difference between the relative amplitude of the responses of the three effectors elicited by stimulation of the cervical sympathetic nerve at frequencies between 0.2 and 2 Hz. Vasoconstrictor responses were relatively larger than membrane contractions suggesting differences in the mechanisms of neurotransmission at the neuroeffector junctions.     

Development of the projection from the nucleus of the brachium of the inferior colliculus to the superior colliculus in the ferret

Neurons in the deeper layers of the superior colliculus (SC) have spatially tuned receptive fields that are arranged to form a map of auditory space. The spatial tuning of these neurons emerges gradually in an experience-dependent manner after the onset of hearing, but the relative contributions of peripheral and central factors in this process of maturation are unknown. We have studied the postnatal development of the projection to the ferret SC from the nucleus of the brachium of the inferior colliculus (nBIC), its main source of auditory input, to determine whether the emergence of auditory map topography can be attributed to anatomical rewiring of this projection. The pattern of retrograde labeling produced by injections of fluorescent microspheres in the SC on postnatal day (P) 0 and just after the age of hearing onset (P29), showed that the nBIC-SC projection is topographically organized in the rostrocaudal axis, along which sound azimuth is represented, from birth. Injections of biotinylated dextran amine-fluorescein into the nBIC at different ages (P30, 60, and 90) labeled axons with numerous terminals and en passant boutons throughout the deeper layers of the SC. This labeling covered the entire mediolateral extent of the SC, but, in keeping with the pattern of retrograde labeling following microsphere injections in the SC, was more restricted rostrocaudally. No systematic changes were observed with age. The stability of the nBIC-SC projection over this period suggests that developmental changes in auditory spatial tuning involve other processes, rather than a gross refinement of the projection from the nBIC.     

A contribution to the study of the architecture of the autonomic nervous system of the digestive tract of the rat

Summary The distribution of aminergic and non-aminergic nerve fibres to the different constituents of the wall of the digestive tract in various regions is described. Aminergic fibres synapse with all nervous perikarya. Densely interlacing networks of nerve fibres are found in both layers of the tunica muscularis and in the lamina muscularis mucosae. A finely meshed plexus is observed in relation to the wall of the blood vessels in the wall of the gut. There are many fibres connecting the muscular and the vascular plexus. No nerve fibres have been observed in direct relation to the epithelium.The functional implications of these findings are discussed.