应激与海马

综述了近年来应激对海马形态和功能影响及海马对应激(HPA轴)调节的研究进展。研究表明,由于海马参与应激的感知、整合与评价,参与HPA轴应激反应,应激影响其结构与功能;而海马又可通过负反馈调节,抑制HPA轴的过度应激反应。但长期慢性应激则可削弱这种抑制作用,加重海马结构与功能的损害。     

Advances and future directions in the study of children's neurobiological responses to trauma and violence exposure

One of the most exciting developments to emerge from the field in the past 20 years is the increasing attention to neurobiological responses to violence and trauma exposure. Although researchers have yet to identify a consensual pattern of neurobiological response to violence and trauma exposure, it does appear that some type of alteration in the hypothalamic pituitary adrenal (HPA) axis is likely. This article briefly reviews the multiple moderating factors that help account for the divergent patterns in HPA function as well as methodological advances that will continue to improve the assessment of HPA function in youth exposed to violence and trauma.     

PTSD,Endophenotypes, the RDoC,and the DSM-5

The search for endophenotypes that stand between genetics and disease has been applied to the diagnostic entity of Posttraumatic Stress Disorder (PTSD). Advances are being made in understanding the pathway to disorder in PTSD in terms of brain regions, neuronal networks, stress-related systems (e.g., the hypothalamic–pituitary–adrenal (HPA) axis), and their underlying genetic and neurogenetic bases. The latter are affected by gene–environmental interactions and epigenetic effects, and the environment and context reciprocally interrelate with them, as well. Therefore, a primary focus on (neuro)pathophysiological intermediates in the disease pathway, as appears emphasized in the research domain criteria (RDoC) approach to etiology of psychiatric disorder, and to which the Diagnostic and Statistical Manual of Mental Disorders 5 (DSM-5) subscribes, might detract from a more inclusive biopsychosocial approach that would be more applicable in the case of PTSD. The paper undertakes a comprehensive review of the recent literature in the areas of endophenotypes, neurogenetics, epigenetics, neural networks, HPA axis, neuronal networks, pathways, the PTSD five-factor model, allostasis, and the RDoC criteria for psychiatric diagnosis, and then returns to the topic of endophenotypes. Neuronal networks constitute one integrating area that could help in arriving at an appropriate model of PTSD endophenotype. Pathway analysis provides a rich field for discerning individual differences in PTSD development, more so than the static approach of using DSM-5 symptom criteria. A model of endophenotypes is presented, which considers these factors in relation to PTSD. The paper concludes with implications for the DSM-5, for practice and for court, especially that it would be premature to seek individual biomarkers of PTSD given the current state of knowledge, even if it is burgeoning.     

Experimental studies on the mechanism of ethanol formation in corpses

Various in vitro experiments were performed for the purpose of clarifying the mechanism of ethanol production in corpses. Whereas a negligible quantity of ethanol was produced in the blood alone, which was left at room temperature, the quantity of ethanol was slightly increased by addition of glucose to the blood. When saprogens were further added, the quantity was markedly increased. Various materials were added to blood-liver homogenates as specimens, and the mixtures were stored in an incubator at 37 degrees C. As a result of the addition of an antibiotic to the mixture every day, there was hardly any production of ethanol. When alcohol dehydrogenase (ADH) and reduced nicotinamide adenine dinucleotide (NADH) were added, ethanol production was slightly increased. When acetaldehyde was added first, ethanol production was inhibited the next day, but on and after day 2, the quantity of ethanol was more than that in the control material. When pyruvic acid was added first, the results were similar to the above. Pyrazole, cyanamide, and disulfiram completely inhibited the production of ethanol. Ethanol production in corpses is believed to take place through a pathway opposite to that of ethanol metabolism in the living body, under the influence of ADH, ALDH, etc., in saprogens using carbohydrates as substrates.     

血小板同种抗原基因中9个单核苷酸多态性在广西地区壮族和汉族人群中的差异分析

目的检测血小板同种抗原基因中9个单核苷酸多态性在广西地区壮族和汉族人群中的差异。方法利用基于单碱基延伸的单核苷酸多态性（SNP）分型芯片,对广西壮族地区99例壮族个体和107例汉族个体的染色体基因组上10个SNP位点进行了分型,其中9个位于6个血小板同种抗原基因中,1个位于基因间区。此外,结合Hapmap计划第二期公布的四个人群的SNP分型数据,分析这六个人群的遗传结构。结果广西原住汉族人在等位基因频率上未检测到与当地壮族有显著性的差异位点,但在基因型频率上,rs630014和rs9441951两位点是显著差异的。广西壮族人与广西汉族、北京汉族人及日本东京人的遗传结构相近,但与祖先来自欧洲西部和北部的犹他州居民以及尼日利亚伊巴丹的约鲁巴人有显著差异的遗传成分存在。结论壮汉两族由于历史上的多次基因交流可能导致其遗传信息在很大程度上是相近的。     

Evaluation of vaginal mRNA markers in women from different age groups: A GeFI collaborative study

Forensic mRNA profiling assays normally include a set of vaginal-specific markers. Although it is known that vagina undergoes characteristic age-related morphological and physiological changes over a lifetime, few studies have evaluated the efficacy of proposed forensic vaginal mRNA markers in women from different age groups.In this collaborative study involving ten GeFI (Italian working group of ISFG) laboratories, a 19-plex mRNA profiling assay including three vaginal-specific markers (CYP2B7P1, MUC4, MYOZ1) was tested in a collection of vaginal swabs obtained from female volunteer donors in their reproductive years (n = 84) and postmenopausa (n = 55).Differential expression of vaginal markers in the two age categories was assessed by means of: a) overall success rate of mRNA profiling (vaginal mucosa “observed” in the tested sample according to scoring protocol) b) average peak height ratios between vaginal-specific markers within mRNA profiling replicates.Other factors potentially influencing mRNA profiling outcomes, like time interval between vaginal swab collection and analysis, concurrence of menstrual cycle and recent sexual activity at the time of sampling were also investigated.     

Estimation of fetal age from dimensions of atlas and axis ossification centers

The atlas and axis ossification centers of 106 human fetal and neonate skeletons were measured. The skeletons belong to the collection in the Department of Forensic Medicine of the Albert Szent-Gy?rgyi Medical University, Szeged, Hungary. The age of the skeletons ranged from 4 to 10 lunar months. Nine linear measurements on the atlas, seven on the axis neural arches ossification centers and three on each one of the axis centra ossification centers were taken. We did simple and multiple linear regression analysis to estimate the age of fetuses. The results show that it is possible to use regression equations to estimate the fetal body length and age from atlas and axis ossification centers measurements during the whole period of development studied. The study of size and shape of the ossification centers using factorial analysis (principal component analysis) shows that the shape of the dens of the axis might be useful to estimate fetal viability.     

RT-PCR检测不同时间大鼠皮肤切创TGF-β_1mRNA表达

目的 探讨TGF-β_1mRNA在不同时间的表达变化及其与伤后经过时间的关系。方法 应用逆转录-聚合酶链反应(RT-PCR)分别对大鼠生前0.5h、1h、3h、6h、12h、48h、72h、96h、168h和死后0.5h、1h、3h的皮肤切创组织中的TGF-β_1mRNA表达变化进行检测,采用ID软件对凝胶扫描的数据进行密度分析。结果 TGF-β_1mRNA在生前皮肤切创后0.5h上升,3h开始急剧升高,48h含量达到峰值;死后皮肤切创未见TGF-β_1mRNA的表达。结论 大鼠皮肤切创TGF-β_1mRNA的表达具有时间相关性,RT-PCR是检测细胞因子在基因水平表达的灵敏方法。     

Tissue-specific differences in mRNA quantification of glucose transporter 1 and vascular endothelial growth factor with special regard to death investigations of fatal injuries

Glucose transporter 1 (GLUT1) and vascular endothelial growth factor (VEGF) have been established as being responsible for cellular adaptation to oxygen deficiency in tissue ischemia and hypoxia mediated by hypoxia-inducible factor 1. We hypothesized that mRNA quantification of these factors in autopsy tissue specimens could have diagnostic significance for investigating the pathology of death, especially after injury. Various cases (total, n=119; less than 48h postmortem) were examined, including fatal blunt injury (n=71) and sharp instrument injury (n=18), as well as asphyxia (strangulation/hanging, n=12) and acute myocardial infarction/ischemia (n=18) as controls. Quantification of mRNA by TaqMan real-time RT-PCR and immunostaining were performed for GLUT1 and VEGF in lung, kidney, and skeletal muscle specimens. The postmortem interval showed no significant influence on the relative quantification of mRNA during the early postmortem period. Characteristic results were found in blunt injury cases: both GLUT1 and VEGF mRNAs decreased in the lung but increased in the skeletal muscle depending on survival time. In the kidney, subacute deaths showed higher GLUT1 mRNA levels compared with acute deaths from blunt injury, but no significant change was found for VEGF mRNA. Immunohistochemistry showed visually predominant GLUT1 immunoreactivity in the renal cortex for cases with a longer survival time, coincident with the results at the mRNA level. Tissue-specific differences in mRNA quantification of GLUT1 and VEGF shed light on tissue ischemia/hypoxia and subsequent tissue-dependent pathophysiological changes leading to death after injury.     

大鼠脑干损伤早期c-fos原癌基因的原位杂交研究

目的　探讨原癌基因c-fos蛋白的表达和脑干早期损伤的关系。方法　 2 0只实验大鼠随机分为脑干损伤组和对照组 ,脑干早期损伤阶段c-fos蛋白表达采用原位杂交组化法观察。结果　对照组大鼠脑干组织未见c-fosmRNA的表达。然而 ,脑干损伤组损伤后 1 0min即可在神经元和胶质细胞观察到c-fosmRNA的表达。且在脑干损伤后 3h内 ,c-fosmRNA的表达程度出现明显的时间依存性。脑干组织死后伤c -fosmRNA的表达亦为阴性。结论　c-fos原癌基因的检测可成为诊断脑干生前损伤的一项指标。     

Fractures of the arches of the atlas: a study of their causation

The autopsy findings in 32 accidental deaths which showed fracture(s) of the arches of the atlas have been correlated to reconstructions of the course of events in the accidents. Flexion of the head causing fracture(s) of the neural arch or odontoid process of the axis also resulted in fracture(s) of the posterior arch due to downward traction. Extension of the head causing fracture of the odontoid process of the axis gave rise to fractures of the posterior arch due to pressure from below. Tilting of the head caused marginal fractures of the anterior arch due to oblique traction. Tilting of the head also caused fracture(s) of the anterior and/or posterior arch due to transverse extension of the atlas ring and/or superior dislocation of one lateral mass in relation to the other. Oblique flexion or extension of the head resulted in similar fractures. Flexion of the head with some rotation combined with compression of the neck can cause the anterior margin of one upper joint surface of the axis to act as a wedge separating the anterior arch of the atlas from below. Extension of the head with some rotation combined with compression of the neck can lead to a fracture running through one lateral mass due to its tilting-dislocation in posterior direction. It is striking that there was no fracture of the atlas which could be ascribed to a simple and symmetric compression of the neck (classical Jefferson's fracture).     

Improving the visibility of tooth cementum annulations by adjustment of the cutting angle of microscopic sections

Age at death assessments by counting tooth cementum annulations (TCAs) in unstained undecalcified microscopic ground sections of (single rooted) teeth is, amongst others, problematic because of the unclear distinction between the bright and darker annulations. Counting is hampered by optical superimposition of the tangentially positioned layers of cementum in the section since 'regular transverse sections' run perpendicular to the axis of a cone-shaped root with its yearly deposited cone-shaped layers of cementum. This study demonstrates that to improve the visibility of the annulations, the cutting angle should be perpendicular to the exterior of a root, not perpendicular to its axis. The site where the cut hits the root perpendicular should show the best possible distinction between the TCAs. Here, superimposition of the now vertical positioned layers within the section will result in increased contrast between bright and darker layers. A procedure for such preparation is given.     

大鼠弥漫性轴索损伤后海马热休克蛋白质70mRNA表达

目的 研究大鼠弥漫性轴索损伤(diffuse axonal injury,DAI)后大脑海马中热休克蛋白质(heat-shockproteins,HSP)70 mRNA的表达变化.方法 采用RT-PCR扩增,扩增产物用琼脂糖凝胶电泳检验,观察DAI后大鼠海马中HSP70 mRNA的表达变化.结果 损伤后4h,大鼠海马中...     

创伤性脑损伤大鼠水通道蛋白4表达变化及法医学意义

目的观察大鼠颅脑损伤后不同时间内水通道蛋白4（AQP4）mRNA表达的变化，探讨AQP4在脑损伤经过时间推断中的意义。方法利用液压冲击法制作不同程度大鼠颅脑损伤模型，在伤后不同时间（0．5、2、6、12、24、48、72h），应用RT-PCR法检测脑组织AQP4 mRNA表达，同时以非损伤组做对照。结果不同程度颅脑损伤后0．5h脑组织AQP4 mRNA表达均开始上调（P〈0．01），6、12h依次增高，24h达到高峰，差异均有统计学意义（P〈0．01），72h时仍维持较高水平（P〈0．01）；0．5h时轻度、中度、重度脑损伤时AQP4 mRNA的表达差异两两之间无统计学意义（P〉0．05），2、6、12、24、48、72h轻度、中度、重度脑损伤时AQP4 mRNA的表达差异两两之间有统计学意义（P〈0．01）。结论颅脑损伤后AQP4 mRNA呈现出时序性变化，其变化规律可望成为法医学推断早期脑损伤时间的指标之一。     

大鼠早期缺血心肌中Basigin mRNA的表达

目的检测Basigin mRNA在大鼠早期缺血心肌和非缺血区心肌中的表达差异及探讨其法医学意义。方法建立大鼠早期心肌缺血手术模型,分为EIM组、NIM组、假手术组以及空白对照组,采用real-time PCR方法检测大鼠心肌缺血后15min、30min、1h和2h Basigin mRNA的表达量。结果与NIM组、假手术组及空白组相比,EIM组BSG mRNA表达量在缺血15min时降低,而冠状动脉结扎1h后表达量降低到SO组的一半,此时具有统计学差异(P0.05),结扎2h后表达量恢复至SO组水平。NIM组、SO组和空白对照组之间表达量无统计学差异(P0.05)。结论心肌急性缺血2小时内BSG mRNA表达降低明显,之后升高,说明BSG参与早期缺血心肌自我保护病理生理过程,提示BSG可用于鉴定早期心肌缺血。     

大鼠死后视网膜细胞mRNA降解与死亡时间的关系研究

目的检测死后大鼠视网膜细胞mRNA的降解和死亡时间(PM I)的关系,为死亡时间推断提供新方法。方法应用复合荧光RT-PCR技术,检测死后不同时间(2、4、6、8、10、12、14、16、18、20、22、24、26、28h)大鼠视网膜细胞β-actin、Pgk1和Rp l 4 mRNA水平,以立即处死大鼠作为对照。方差检验比较组间差异,并对所得数据进行回归分析。结果死后28h内,大鼠视网膜细胞β-actin、Pgk1、Rp l 4 mRNA水平均随死亡时间的延长而下降。3个管家基因mRNA的降解与死亡时间的线性拟合回归方程分别为:Yβ-actin=-4436.205Xβ-actin+127581.7(r2=0.976),YPgk1=-1993.884XPgk1+57651.54(r2=0.973),YRp l 4=-1189.791XRp l 4+34533.46(r2=0.955)。结论大鼠死后视网膜细胞mRNA的含量随着死亡时间的延长而逐渐降解,与死亡时间具有相关性。     

大鼠急性心肌缺血后肌浆网RyR2 mRNA表达变化

目的 研究大鼠急性心肌缺血后心肌肌浆网兰尼碱受体蛋白2(ryanodine receptor 2,RyR2)mRNA表达的变化.方法 将SD大鼠分为正常对照组、心肌缺血组和缺血性猝死组.采用腹腔注射垂体后叶素的方法复制大鼠急性心肌缺血和猝死模型,对心肌进行半定量荧光RT-PCR检测,观察RyR2 mRNA表达水平的变化.结果 与正常对照组相比,不同时间和不同程度的急性心肌缺血后心肌肌浆网RyR2 mRNA表达均显著降低(P<0.05).结论 心肌缺血性损伤可诱导心肌钙调控蛋白RyR2 mRNA表达下调.