慢性氟、砷染毒对小鼠肾皮质氧化应激的损害

目的　探讨慢性氟中毒、砷中毒及联合中毒对小鼠肾皮质氧化应激损害程度及其异同 ,为氟、砷中毒的防治提供科学依据。方法　昆明种小鼠 1 2 0只 ,随机分成对照、氟、砷和氟砷联合染毒 4组 ,分别自由进食普通、高氟、高砷和高氟高砷饲料 ,分别于 6个月和 1 2个月取材 ,检测肾皮质丙二醛 (MDA)和脂质过氧化物 (LPO)含量、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶 (GSH PX)、琥珀酸脱氢酶 (SDHase)和葡萄糖 6 磷酸酶 (G 6 Pase)活力。结果　与对照组比较 ,3种染毒模式在 6和 1 2个月观察期均引起肾皮质MDA含量增加 (P <0 0 1 ) ,GSH PX 活力在 6个月时均下降 (P <0 0 1 ) ;仅见氟组在 1 2个月时恢复正常 ,而砷和氟 +砷组仍维持低水平 (P <0 0 1 ) ;2个观察时点的SOD活力均下降 (P <0 0 1 )。此外 ,1 2个月的GSH、SDH和G 6 Pase均下降 (P <0 0 1 ,P <0 0 1 ,P <0 0 5)。结论　慢性氟、砷和氟砷联合染毒均能引起小鼠肾皮质氧化应激作用增强 ,氟、砷 2毒物对在引起肾皮质LPO损害作用方面无明显交互作用     

热暴露对小鼠红细胞免疫粘附功能的影响

热暴露对小鼠红细胞免疫粘附功能的影响武警医学院（天津３００１６２）叶路董小青韩景田邢杰周景峰近年来，有关高热对机体免疫功能影响的研究越来越受到人们的重视。有研究报道，一次性温度超过３９℃，可导致机体细胞免疫与体液免疫的全面抑制。本实验采用补体致敏酵母...     

砷对小鼠子代神经行为发育的影响

砷污染环境对人体健康的影响已引起人们高度重视,许多学者对此进行了大量研究。但关于砷的行为畸胎学方面的研究报道甚少。本研究采用一组神经行为功能测试方法,观察了孕鼠染砷对仔鼠神经行为发育的影响,以便为全面评价砷的发育毒性提供依据。     

大气颗粒物暴露致miR-150缺失小鼠海马神经炎症损伤的作用研究

目的探讨miR-150缺失在大气颗粒物暴露致小鼠神经炎症损伤的作用。方法 SPF级雄性C57BL/6J野生型及miR-150敲除C57BL/6J小鼠各30只,分为C57野生型清洁空气组(C57BL/6J组)、C57野生型常规空气暴露组(C57BL/6J+PM组)、miR-150敲除清洁空气组(miR-150ko组)及miR-150敲除常规空气暴露组(miR-150ko+PM组),每组15只。清洁空气组放置独立送回风净化笼具(Individual ventilation cages,IVC)饲养,常规空气组放置于常规空气饲养,实验期共12个月。应用旷场试验、新物体识别实验检测小鼠行为学变化,采用生物素双抗体夹心酶联免疫吸附法(Enzyme linked immunosorbent assay,ELISA)的方法检测小鼠海马中BDNF及炎症因子(TGF-β、IFN-γ、IL-4及IL-17)变化。结果整个实验期间常规空气中PM_2.5的平均质量浓度为99.81μg/m³,IVC笼中洁净空气组PM_2.5的平均质量浓度为1.24μ...     

砷对机体抗氧化能力的影响及硒多糖的拮抗作用

地方性砷中毒 (简称地砷病 )是一种严重危害人体健康的地方病。山西是我国继新疆、内蒙之后发现的第 3个饮水型地砷病病区。 1994年在大同地区 5个县共查出病人 3 0 0 0余例 ,病区人口达 10 0多万人。目前有关砷中毒的毒作用机制还未有定论 ,其中的脂质过氧化学说近年来受到了一定关注。本研究对染砷大鼠和砷中毒病区人群的抗氧化能力进行测定 ,以探讨抗氧化作用在砷中毒发病中的意义 ;同时对硒多糖的拮抗效果进行了观察 ,为进一步探讨砷中毒的防治提供依据。1　材料与方法1 1　动物分组及染毒　选用山西医科大学动物中心提供的健康Ｗｉｓｔ…     

三氧化二砷对小鼠免疫功能的影响

三氧化二砷对小鼠免疫功能的影响刘佳吴克枫俞红李锦兰高敏（贵州省卫生防疫站，贵阳５５０００４）用Ａｓ２Ｏ３染毒昆明种雌性小鼠，采用０．１，０．７，４ｍｇｋｇ－１３个剂量组，以２５ｍｇｋｇ－１的环磷酰胺作为阳性对照，经口连续染毒２２ｄ观察Ａｓ２Ｏ３对小鼠...     

硝酸镧亚急性暴露对C57-ras转基因小鼠神经行为学及海马细胞形态学的影响

目的 研究硝酸镧亚急性暴露对C57-ras转基因小鼠神经行为和海马细胞形态学的影响,初步探索ras基因在镧对小鼠海马结构与功能毒性效应中的保护作用.方法 40只C57-ras转基因小鼠随机分为4组(雌雄各半),分别灌胃0、12.5、25和50 mg/kg·bw剂量的硝酸镧六水合物(以镧计算,分别为:4.01、8.02和...     

新生小鼠小脑提取液对成年小鼠神经干细胞分裂与增殖的影响

目的:探讨新生小鼠小脑提取液(ECNM)对成年小鼠脑内神经干细胞分裂与增殖的影响.方法:采用脑立体定位给药技术,将ECNM注入前脑和海马,应用Nestin单抗做免疫组化染色,显示神经干细胞.结果:给予ECNM后7d和14d,在前脑和海马均可见密集的神经干细胞,对照组未见阳性染色.结论:ECNM可诱导成年小鼠神经干细胞分裂与增殖.     

松花粉对砷中毒小鼠肾脏细胞调亡的影响

目的:通过研究松花粉对砷中毒小鼠肾脏细胞凋亡恢复情况,来检测松花粉对砷中毒小鼠的肾脏细胞的作用。方法:将54只小鼠随机分为3组:即A组(正常对照组)、B组(治疗组)、C组(NaAsO2对照组)。正常对照组饮用蒸馏水;治疗组、NaAsO2对照组均隔天注射NaAsO2(3 mg/kg)进行砷染毒,治疗组在砷染毒进行的第15天后开始用松花粉灌胃(1 g/kg,用水稀释至0.6 mL/只)。至第45天,用细胞凋亡因子定量酶联检测试剂盒检测各组肾脏细胞促细胞凋亡因子sFas/APO-1表达量。结果:A,B,C三组肾脏细胞sFas/APO-1表达量分别为:18.273 ng/mL,23.404 ng/mL,62.202 ng/mL.NaAsO2 NaAsO2对照组与治疗组相比凋亡量显著增加(P<0.05);NaAsO2对照组与正常对照组相比,凋亡量极显著增加(P<0.01)。结论:松花粉能降低砷中毒后小鼠肾脏细胞凋亡。     

不同产地当归中砷暴露对小鼠肝肾毒性损伤的研究

目的研究不同产地当归中重金属砷暴露对小鼠肝肾的损伤情况,并探讨其毒性.方法35只昆明种成年小鼠随机分为正常对照组、当归组(产地分别为云南、四川和陕西)和雄黄组共5组.小鼠灌胃给药72h 后处死,取血,肝脏和肾脏组织,全自动生化分析仪检测血清丙氨酸转氨酶(ALT)、天门冬氨酸转氨酶(AST)、尿素氮(UREA)和肌酐(CREA)含量,观察肝肾组织病理学变化;原子荧光光谱测定肝肾组织中的砷蓄积量;实时荧光定量(RT-PCR)检测砷毒性敏感基因金属硫蛋白-1(Metallothionein,MT-1)mRNA 和肿瘤坏死因子-α(TNF-α)mRNA 的表达水平.结果与对照组相比,雄黄组血清 ALT、AST、CREA 浓度水平和肝肾组织中砷蓄积量显著升高(P<0.05),并可能伴随肝肾功能的损伤, MT-1 mRNA 和 TNF-αmRNA 表达量升高但无统计学意义.当归组只在肝组织中检测到微量砷,肝肾功能病理学检查与正常对照组相似,MT-1 mRNA 和 TNF-αmRNA 表达量无显著升高(P>0.05).结论不同产地当归所含砷的毒性远小于雄黄毒性,高剂量雄黄给药对小鼠肝肾组织可能产生影响,但它们在一定剂量下被用于中药仍然是相对安全的.     

Effects of arsenic trioxide inhalation exposure on pulmonary antibacterial defenses in mice

The effects of single and multiple (5 and 20) 3-h inhalation exposures to aerosols of arsenic trioxide on the pulmonary defense system of mice were investigated. Arsenic trioxide mist was generated from an aqueous solution and dried to produce particulate aerosols of 0.4 micron mass median aerodynamic diameter. Aerosol mass concentration ranged from 125 to 1000 micrograms As/m3. Effects of the exposures were evaluated by determination of changes in susceptibility to experimentally induced streptococcal aerosol infection and in pulmonary bactericidal activity to 35S-labeled Klebsiella pneumoniae. Significant increases in mortality due to the infectious challenge and decreases in bactericidal activity were seen after single 3-h exposures to 270, 500, and 940 micrograms As/m3. Similarly, 5 or 20 multiple 3-h exposures to 500 micrograms As/m3 produced consistently significant increases in mortality and decreases in pulmonary bactericidal activity. At 125 or 250 micrograms As/m3, a decrease in bactericidal activity was seen only after 20 exposures to 250 micrograms/m3. Results from earlier studies with an arsenic-containing copper smelter dust were compared to these data. The possibility of the development of adaptation during multiple exposures to arsenic trioxide is also considered.     

Gas chromatography‐mass spectrometry based metabolomics profile of hippocampus and cerebellum in mice after chronic arsenic exposure

Intake of arsenic (As) via drinking water has been a serious threat to global public health. Though there are numerous reports of As neurotoxicity, its pathogenesis mechanisms remain vague especially its chronic effects on metabolic network. Hippocampus is a renowned area in relation to learning and memory, whilst recently, cerebellum is argued to be involved with process of cognition. Therefore, the study aimed to explore metabolomics alternations in these two areas after chronic As exposure, with the purpose of further illustrating details of As neurotoxicity. Twelve 3‐week‐old male C57BL/6J mice were divided into two groups, receiving deionized drinking water (control group) or 50 mg/L of sodium arsenite (via drinking water) for 24 weeks. Learning and memory abilities were tested by Morris water maze (MWM) test. Pathological and morphological changes of hippocampus and cerebellum were captured via transmission electron microscopy (TEM). Metabolic alterations were analyzed by gas chromatography‐mass spectrometry (GC‐MS). MWM test confirmed impairments of learning and memory abilities of mice after chronic As exposure. Metabolomics identifications indicated that tyrosine increased and aspartic acid (Asp) decreased simultaneously in both hippocampus and cerebellum. Intermediates (succinic acid) and indirect involved components of tricarboxylic acid cycle (proline, cysteine, and alanine) were found declined in cerebellum, indicating disordered energy metabolism. Our findings suggest that these metabolite alterations are related to As‐induced disorders of amino acids and energy metabolism, which might therefore, play an important part in mechanisms of As neurotoxicity.     

Effects of exposure to nanoparticle-rich diesel exhaust on adrenocortical function in adult male mice

To investigate the effects of nanoparticle-rich diesel exhaust (NR-DE) on adrenocortical function, seven-week-old male mice were divided into four groups and exposed to either whole NR-DE at low (41.73 μg/m³, 8.21 × 10⁵ particles/cm³), high (152.01 μg/m³, 1.80 × 10⁶ particles/cm³) concentrations, filtered diesel exhaust (F-DE) or clean air for 8 weeks (5 h/day, 5 days/week). After 8 weeks of exposure, the animals were euthanized under pentobarbital anesthesia and the blood samples were collected to detect serum progesterone and corticosterone. In addition, adrenal glands were excised, and adrenal cells were cultured in the absence or presence of rat adrenocorticotropic hormone (ACTH) (10⁻¹⁵ to 10⁻¹⁰ M) for 4 h. There were no significant differences in the body weight, absolute and relative adrenal gland weight among the groups. Serum concentration of corticosterone and progesterone was not changed significantly. Administration of ACTH resulted in a dose-dependent increase in corticosterone and progesterone release in mice-exposed to low-concentration NR-DE and clean air. Moreover, corticosterone and progesterone concentrations in adrenal cells increased significantly in mice-exposed to low-concentration NR-DE basal and administrated with ACTH (10⁻¹⁵ to 10⁻¹¹ M for corticosterone; 10⁻¹⁴ to 10⁻¹¹ M for progesterone) compared with the control mice. In contrast, the concentration of corticosterone and progesterone decreased significantly in mice-exposed to high-concentration NR-DE or F-DE basal and administrated with ACTH (10⁻¹² to 10⁻¹⁰ M for corticosterone; 10⁻¹⁵ to 10⁻¹⁰ M for progesterone) compared with the control mice. These results suggest that exposure to NR-DE or F-DE may disrupt adrenocortical function in adult male mice.     

Effects of arsenic exposure from drinking water on spatial memory,ultra-structures and NMDAR gene expression of hippocampus in rats

Epidemiological investigations indicate that chronic arsenic exposure can damage neurobehavioral function in children. The present study was aimed to study the effects of arsenic exposure from drinking water on the spatial memory, and hippocampal ultra-structures and N-methyl-d-aspartate receptor (NMDAR) gene expression in rats. Sprague–Dawley rats were assigned to four groups: rats in control group drank regular water, rats in other groups drank water with final arsenic concentration of 2.72 mg/L (group A), 13.6 mg/L (group B) and 68 mg/L (group C), respectively, for 3 months. The levels of arsenic in blood serum and hippocampus were monitored. Rats were tested in Morris water maze (MWM) for memory status. Samples of hippocampus were collected from two rats in each group for transmission electron microscopic study and the detection of NMDAR expression by RT-PCR. The rats in group C showed a significant delay in hidden platform acquisition. Neurons and endothelial cells presented pathological changes and the expression of NR2A was down-regulated in hippocampus in arsenic exposed rats. Our data indicated that arsenic exposure of 68 mg/L caused spatial memory damage, of which the morphological and biochemical bases could be the ultra-structure changes and reduced NR2A expression in hippocampus.     

Pubertal exposure to Bisphenol A increases anxiety-like behavior and decreases acetylcholinesterase activity of hippocampus in adult male mice

The negative effects of Bisphenol A (BPA) on neurodevelopment and behaviors have been well established. Acetylcholinesterase (AChE) is a regulatory enzyme which is involved in anxiety-like behavior. This study investigated behavioral phenotypes and AChE activity in male mice following BPA exposure during puberty. On postnatal day (PND) 35, male mice were exposed to 50 mg BPA/kg diet per day for a period of 35 days. On PND71, a behavioral assay was performed using the elevated plus maze (EPM) and the light/dark test. In addition, AChE activity was measured in the prefrontal cortex, hypothalamus, cerebellum and hippocampus. Results from our behavioral phenotyping indicated that anxiety-like behavior was increased in mice exposed to BPA. AChE activity was significantly decreased in the hippocampus of mice with BPA compared to control mice, whereas no difference was found in the prefrontal cortex, hypothalamus and cerebellum. Our findings showed that pubertal BPA exposure increased anxiety-like behavior, which may be associated with decreased AChE activity of the hippocampus in adult male mice. Further studies are necessary to investigate the cholinergic signaling of the hippocampus in PBE induced anxiety-like behaviors.     

Effect of prenatal ultrasound exposure on adult behavior in mice

Pregnant Swiss mice were exposed to diagnostic levels of ultrasound (3.5 MHz, Maximum acoustic output: I_SPTP = 1 W/cm² and I_SATA = 240 mW/cm², acoustic power = 65 mW) min on days 11.5 or 14.5 postcoitus (PC). At 3 and 6 months postpartum, offspring were subjected to the following behavioral tests: bright and dark arena test for locomotor/exploratory activity and passive avoidance test for learning and memory. Anxiolytic activity and latency in learning were noticed in the ultrasound-treated animals. The effect was more pronounced in the 14.5 days PC group than in the 11.5 days PC group. But memory was not affected in the ultrasound-exposed animals. There was a nonsignificant decrease in the total locomotor activity at 6 months of age in all the exposed animals. Thus, the present data demonstrate that exposure to diagnostic ultrasound during late organogenesis period or early fetal period in mice may cause changes in postnatal behavior as evidenced by selected adult offspring behavioral tests. However, any conclusive statement in this regard should await results from more detailed investigations.     

Napoleon Bonaparte's exposure to arsenic during 1816

Summary Analysis of hair from Napoleon showed that he was exposed to considerable amounts of arsenic during 1816. The distribution pattern of the arsenic in the hair is similar to that found after the daily ingestion of excessive amounts of arsenic.

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Zusammenfassung Die Analyse, die am Haar Napoleons vorgenommen wurde, hat nachgewiesen, daß er im Laufe des Jahres 1816 erheblichen Mengen von Arsen ausgesetzt war. Das Erscheinungsbild der Verteilung des Arsens gleicht demjenigen, das sich nach täglicher Einnahme übermäßiger Mengen von Arsen ergibt.

     

Subhepatotoxic exposure to arsenic enhances lipopolysaccharide-induced liver injury in mice

Exposure to arsenic via drinking water is a serious health concern in the US. Whereas studies have identified arsenic alone as an independent risk factor for liver disease, concentrations of arsenic required to damage this organ are generally higher than found in the US water supply. The purpose of the current study was to test the hypothesis that arsenic (at subhepatotoxic doses) may also sensitize the liver to a second hepatotoxin. To test this hypothesis, the effect of chronic exposure to arsenic on liver damage caused by acute lipopolysaccharide (LPS) was determined in mice. Male C57Bl/6J mice (4-6 weeks) were exposed to arsenic (49 ppm as sodium arsenite in drinking water). After 7 months of exposure, animals were injected with LPS (10 mg/kg i.p.) and sacrificed 24 h later. Arsenic alone caused no overt hepatotoxicity, as determined by plasma enzymes and histology. In contrast, arsenic exposure dramatically enhanced liver damage caused by LPS, increasing the number and size of necroinflammatory foci. This effect of arsenic was coupled with increases in indices of oxidative stress (4-HNE adducts, depletion of GSH and methionine pools). The number of apoptotic (TUNEL) hepatocytes was similar in the LPS and arsenic/LPS groups. In contrast, arsenic pre-exposure blunted the increase in proliferating (PCNA) hepatocytes caused by LPS; this change in the balance between cell death and proliferation was coupled with a robust loss of liver weight in the arsenic/LPS compared to the LPS alone group. The impairment of proliferation after LPS caused by arsenic was also coupled with alterations in the expression of key mediators of cell cycle progression (p27, p21, CDK6 and Cyclin D1). Taken together, these results suggest that arsenic, at doses that are not overtly hepatotoxic per se, significantly enhances LPS-induced liver injury. These results further suggest that arsenic levels in the drinking water may be a risk modifier for the development of chronic liver diseases.     

小鼠孕期染镉对子代免疫功能的影响

小鼠在受孕第９～１５天给予氯化镉灌胃，剂量分别为０，１．０，１０．０ｍｇ／ｋｇ，检测其仔鼠在４和８周龄对各项免疫功能的变化。结果发现，从时间上来看，仔鼠外周血白细胞总数、Ｔ淋巴细胞计数和血清溶血素滴度在８周龄时低剂量组有刺激作用，在４周龄时均无影响，表现出迟发作用；从剂量上看，８周龄时上述指标均为低剂量有刺激作用，高剂量无影响。而血清溶菌酶是在４周龄时高剂量组有抑制趋势。母鼠产后２１天肝肾内有明显的镉蓄积，仔鼠胸腺、脾、肝、肾中却未见明显镉蓄积，说明镉对仔鼠免疫功能的影响不是直接作用所致