贫铀对大鼠肺诱导型一氧化氮合酶基因表达的影响

目的通过研究贫铀(depleted uranium,DU)颗粒气管灌注大鼠肺中的诱导型一氧化氮合酶(iNOS)基因表达的变化,揭示DU对肺组织的毒性作用机制。方法Wistar大鼠20只随机分为4组,1个对照组,3个染铀组,剂量分别为1、3、5 mg/ml气管灌注不同剂量DU颗粒3个月后,将大鼠肺组织iNOS mRNA进行RT-PCR并通过凝胶成像分析系统扫描RT-PCR产物,用内参半定量法分析iNOS mRNA的变化。结果对照组无iNOS mRNA表达,各染铀组扩增产物电泳条带吸光度值(A)明显高于对照组(P<0.05);其中13、mg组产物电泳条带A值逐渐增高,3 mg组到达高峰,5 mg组产物电泳条带A值明显低于13、mg组(P<0.05)。结论DU颗粒气管灌注能使大鼠肺组织iNOS mRNA表达水平升高,并与DU剂量呈正相关。DU剂量增高到一定程度则使iNOS mRNA表达水平降低,这种变化可能与DU化学毒性和辐射损伤的复合作用有关。     

Schneeberg lung disease and uranium mining in the saxon ore mountains (Erzgebirge)

The so-called Schneeberg lung disease is a form of bronchial or alveolar carcinoma caused by the effects of the radioactive gas radon and of its radioactive short half-life daughter products. This type of radiation-induced occupational cancer is the most common and the most important radiation injury among workers occupationally exposed to ionizing radiation. There have been many deaths from lung cancer, especially in the Soviet uranium mines in the Erzgebirge of Saxony in the former German Democratic Republic. The history of disease in these miners extends over five centuries; the first observations of their health hazard start in the Middle Ages. The discovery of the lung cancer component was made toward the end of the nineteenth century, and the suspicion that a connection might exist between this cancer type and exposure to ionizing radiation was voiced at the beginning of the twentieth century. In the first half of this century, further research was carried out on this disease in the Schneeberg area of the Erzgebirge. Before the end of World War II, guidelines were set up to define the acceptable limits of radon exposure in the ore mines of Saxony. After World War II, the American uranium mines in the Colorado Plateau used the German research results as a basis for working out their own radiation protection standard. The uranium mines under Soviet occupation in the former GDR, on the contrary, paid no attention to these research findings. For many years, no precautions were taken for the miners' working conditions. The consequence of this serious omission was an estimated 9,000 fatal cases of lung cancer among these underground miners. High concentrations of radon are to be found in indoor air of homes in some districts of the Erzgebirge, suggesting an increasing lung cancer risk for the local inhabitants. The significance of this finding is evaluated. © 1993 Wiley-Liss, Inc.     

浓缩铀诱发体细胞和生殖细胞的放射遗传毒理效应

为了解浓缩铀对人体的危害, 本文研究了浓缩铀诱发体细胞和生殖细胞的遗传毒理效应。结果表明:浓缩铀UO₂F_{2诱发体细胞的突变效应是:可导致骨漪细胞和外周血淋巴细胞的染色体畸变发生。同时细胞分裂指数亦受到明显抑制.而诱发生殖细胞的突变效应是:对精原细胞主要诱发染色体断片,而在初级精母细胞中观察到多价体发生,传递遗传损害.对雄性生殖细胞DNA损伤,观察到以受²³⁵U作用后12天的精子DNA洗脱率最高,对所致DNA链断裂程度之间呈现线性剂量效应关系.实验还观察到精子畸形,并随着精子发育阶段的不同而呈现不同程度的损伤效应.尤其在注入后的13天和36天阶段,精子畸形率呈显著增升.}     

二甲亚砜对染毒支气管上皮细胞的保护作用分析

目的在观察铀矿粉对体外培养的支气管上皮细胞的毒性作用同时,加入二甲亚砜,以了解其在支气管上皮细胞受铀矿粉染毒时的可能保护机制。方法将不同浓度的铀矿粉与体外培养的支气管上皮细胞进行长时间接触,分为对照组、染毒组和二甲亚砜（DMSO）保护组,通过血清抗性实验等,观察各组间细胞受损的情况。结果随着铀矿粉浓度的增高,支气管上皮细胞受损明显加重,加入二甲亚砜的支气管上皮细胞受损情况好于未加入者。DMSO对铀矿尘作用于BEAS-2B细胞后,可引起细胞DNA断裂,造成细胞拖尾率、彗星尾部DNA含量、尾长、尾部面积、尾距增加具有较好的抑制作用。结论铀矿粉对支气管上皮细胞有明显的恶性转化作用,可能是铀矿粉对肺损伤的主要机制,二甲亚砜具有一定的保护作用。     

含邻苯二酚基团的黄酮化合物促排急性贫铀中毒效果的研究

目的 寻找对急性贫铀中毒促排效果较好的含邻苯二酚基团的黄酮类化合物.方法 给予Wistar大鼠贫铀20 mg/kg,立即给予黄酮类化合物10 mg/kg,连续3 d,并设邻苯二酚类化合物8102及DMSO做为对照.3 d后做肾功能检测和肾脏、肝脏、骨髓、脾脏等病理观察.结果 8102和F1组血清肌酐和尿素氮含量显著下降,F2、T1和T2组的肌酐浓度也显著降低.病理观察显示,T2组肾脏、肝脏几乎无明显损伤;8102和T1次之;F1和QU 组肾损伤较重;DMSO组的损伤最重,但较贫铀组轻.结论 T2对贫铀敏感器官的保护最好;F1可改善肾功能.这两种化合物均具有做为贫铀促排剂的潜能.     

长期摄入低剂量贫铀对大鼠血象与肝肾功能的影响

目的研究长期摄入低剂量贫铀对大鼠的血象、肝肾功能的影响。方法给予初断乳大鼠含贫铀饲料,摄入贫铀的剂量分别为0、0.4、4、40mg·kg-1·d-1,随后的14个月内,临床生化自动检测仪测定外周血、肝肾功能的变化。结果F0代:小剂量组在14个月、中剂量组在10个月、高剂量组在7个月;F1代:中、高剂量组在10个月时出现白细胞显著降低,并由这些时相点开始出现各项血液学指标持续下降。随摄入贫铀剂量的增加,摄入时间的延长,白细胞和红细胞计数出现下降的时间越早,降幅越大;同一剂量组同一时相点,F1代比F0代降得更低。实验组肝功能与正常组没有显著差异(P>0.05)。肾功能指标仅有某个时相点血清肌酐上升,其余变化不显著(P>0.05)。结论长期摄入低剂量贫铀,只有在较长期或剂量较大时,可使外周血白细胞下降,继而红细胞、血小板计数下降;肾功能影响轻微,肝功能无影响。     

ApoE4 impairs hippocampal plasticity isoform-specifically and blocks the environmental stimulation of synaptogenesis and memory

Alzheimer's disease (AD) is associated with genetic risk factors, of which the allele E4 of apolipoprotein E (apoE4) is the most prevalent, and is affected by environmental factors that include education early in life and socioeconomic background. The extent to which environmental factors affect the phenotypic expression of the AD genetic risk factors is not known. Here we show that the neuronal and cognitive stimulations, which are elicited by environmental enrichment at a young age, are markedly affected by the apoE genotype. Accordingly, exposure to an enriched environment of young mice transgenic for human apoE3, which is the benign AD apoE allele, resulted in improved learning and memory, whereas mice transgenic for human apoE4 were unaffected by the enriched environment and their learning and memory were similar to those of the nonenriched apoE3 transgenic mice. These cognitive effects were associated with higher hippocampal levels of the presynaptic protein synaptophysin and of NGF in apoE3 but not apoE4 transgenic mice. In contrast, cortical synaptophysin and NGF levels of the apoE3 and apoE4 transgenic mice were similarly elevated by environmental enrichment. These findings show that apoE4 impairs hippocampal plasticity and isoform-specifically blocks the environmental stimulation of synaptogenesis and memory. This provides a novel mechanism by which environmental factors can modulate the function and phenotypic expression of the apoE genotype.     

丰富环境对大鼠学习记忆及海马CA1区脑源性神经营养因子表达的影响

目的 探讨丰富环境对Wistar大鼠学习记忆的影响及其脑源性神经营养因子(BDNF)机制.方法 20只3周龄Wistar大鼠随机分为丰富环境组和正常对照组,分别在丰富环境和正常环境喂养30d.Morris水迷宫实验评定其学习记忆能力,免疫组化检测海马CA1区BDNF的蛋白表达.结果 丰富环境组大鼠逃避潜伏期[(24.37±5.45)s]显著短于对照组[(31.28±5.39)s],差异具有显著性(P<0.05);丰富环境组跨越平台次数[(3.38±0.79)次]、平台象限游泳距离[(915.52±125.12)cm]明显多于对照组[(2.21±0.49)次、(468.67±70.29)cm],差异具有显著性(P<0.01);丰富环境组海马CA.区BDNF灰度值(128.79±8.45)明显小于正常对照组(142.57±9.36),差异具有显著性(P<0.05).结论 丰富环境明显增强大鼠的学习记忆能力,其可能是通过BDNF机制实现的.     

Effects of differential environments on recovery from neonatal brain lesions,measured by problem-solving scores and brain dimensions

To study effects of differential experience on recovery from brain lesions and on gross anatomy of the brain, we ran two experiments with rats of the Berkeley S₁ strain. On the day of birth, some animals received lesions directed to the occipital cortex, but in many cases subcortical damage also resulted; other animals were sham-operated. In Experiment 1, half the rats lived in restricted environments and half in enriched environments from Day 5 or 6 until about Day 65; in Experiment 2 the differential environments were begun on Day 25 and lasted until Day 65. The rats were then pretrained and tested on the standard 12 Hebb-Williams problems. Both experiments yielded significant overall effects of brain status (lesion vs. control) and of environment (impoverished vs. enriched). The effects of environment were larger in Experiment 2 where the lesions were smaller than in Experiment 1. Considerable generality was demonstrated for the beneficial effects of environment on behavioral recovery since it was obtained with both sexes, with large lesions in Experiment 1 and with relatively small lesions in Experiment 2, with both immediate and delayed environmental therapy, and with shorter periods of enriched experience than had been employed previously. The enriched experience benefits brain injured rats even though their learning ability is impaired. The length and width of the cerebral hemispheres were also found to be affected by lesions and, to a lesser extent, by environmental treatment.     

Mass training of rats in a superenriched environment

A training apparatus for rats is described that allows the simultaneous training of 70 animals without requiring much effort from the experimenter. The apparatus is based on the enriched environment as devised by Bennett et al. [1] but is superior to the original in that it confronts the rats with true learning situations. For example, the animals will learn to traverse a maze and to select and open appropriate gates in order to get access to either food or water. The number of tasks and their complexity are gradually increased during a training period of 29 days. The apparatus offers a convenient means for supplying the investigator with a large number of trained animals in studies aimed at correlating behavior with brain morphology and biochemistry.