染铝大鼠学习记忆及脑单胺类神经递质含量的变化

目的观察三氯化铝(AlCl3)对大鼠学习记忆及脑中枢单胺类神经递质含量变化的影响,为探讨铝的神经毒性作用机制提供依据.方法 144只Wistar大鼠随机分为注射剂量分别为5.0、15.0、25.0 mg/kg的3个剂量组和生理盐水对照组.在染毒4、8、12周时分批进行大鼠跳台实验,用荧光法测定各脑区内单胺类神经递质含量.结果各时间剂量组大鼠主动回避次数显著下降,被动逃避延迟时间显著延长,差异均有显著性(P<0.01);各时间剂量组多巴胺(DA)和去甲肾上腺素(NE)含量均呈梯度下降趋势,差异有显著性(P<0.01).除5.0 mg/kg组4周和8周时大脑5-羟色胺(5-HT)和海马5-羟吲哚乙酸(5-HIAA)含量无变化外,其他各时间剂量组的5-HT和5-HIAA含量均呈梯度下降,差异均有显著性(P<0.01).结论实验结果表明,铝可影响学习记忆能力,铝能导致各脑区单胺类神经递质含量下降且作用部位有选择性,这可能是铝的神经毒性作用机制之一.     

甲基汞对亲仔两代大鼠的神经行为毒性效应

目的探讨大鼠妊娠期甲基汞暴露的母体毒性及对仔代的神经行为毒性效应。方法Wistar孕鼠52只于妊娠第6～9天用甲基汞0.00、0.01、0.05、2.00mg/(kg·d)连续灌胃。分别观察母体毒性 ;常规致畸实验 ;记录205只仔鼠早期生理发育和神经行为发育指标 ;10周龄仔鼠32只进行程序控制行为测试 ;分娩后5周母鼠和10周龄仔鼠各24只进行脑组织形态学观察和单胺类神经递质的测定。实验遵循随机、双盲原则。结果未观察到母体毒性和仔代形态畸形 ;3个暴露组胎仔的体重、尾长低于对照组 (P<0.01) ;各暴露组仔鼠体重增长、早期生理及神经行为发育滞后于对照组 (P<0.05) ;程序控制行为学习成绩比对照组降低 (P<0.05) ,有剂量_效应关系 (rs= -0.7273 ,P<0.01) ;各暴露组母鼠和仔鼠脑组织无形态学改变 ,但单胺类神经递质含量均比对照组显著增高 (P<0.05) ,有剂量_效应关系 (rs=0.7124～0.9257 ,P<0.01)。结论本研究剂量的妊娠期甲基汞暴露未观察到对孕鼠的毒性效应 ,但有轻度胚胎毒性 ,影响仔鼠的神经系统发育 ,导致仔鼠学习记忆能力降低 ,亲仔两代大鼠脑组织中单胺类神经递质的含量增高     

锰职业接触工人生物标志物的研究

目的 探讨锰接触工人个体实际接触剂量与生物指标之间的关系,以寻找合适的早期生物学监测指标.方法 选择济南市某机车车辆厂电焊作业工人270名,收集其血液和尿液.原子吸收光谱法测定血锰、尿锰和个体锰接触剂量;高效液相色谱荧光法测定尿中高香草酸(HVA)和香草扁桃酸(VMA);对各指标进行相关性分析.结果 个体锰接触剂量(CTWA)为0.005 5～1.957 7mg/m3,平均浓度为(0.25±0.31)mg/m3;接锰工人尿锰浓度为0.011 2～2.447 2μg/mg Cr,平均(0.22±0.31)μg/mg Cr;血锰浓度为0.06～38.70 μg/ml,平均(3.94±6.66)μg/ml;尿HVA浓度为0.102～4.780 μg/mg Cr,平均(1.01±0.78)μg/mg Cr;VMA浓度为0.032～2.768 μg/mg Cr,平均(0.61±0.35)μg/mg Cr.个体锰接触剂量与血锰、尿锰、尿中VMA之间均无相关性(P＞0.05);个体锰接触剂量与尿中HVA呈负相关,差异有统计学意义(r=-0.168,P＜0.01).结论 血锰、尿锰、尿中VMA均不能作为评价锰接触的接触生物标志物;尿中HVA可以作为评价锰接触的效应生物标志物.     

测定尿高香草酸含量对早期诊断锰中毒的意义

本文对某客车厂车体车间157名锰作业者测定了尿高香草酸(HVA)含量。结果表明:尿HVA含量接触组明显低于对照组,(P<0.01)。以对照组为正常人群计算尿HVA正常值下限为3.13mmol/mol肌酐。接触组尿HVA低于正常值下限阳性率明显高于对照组(P<0.01)。     

无铅汽油对神经行为功能和单胺类神经递质代谢产物的影响

目的 探讨职业性无铅汽油接触以对神经功能和单胺类神经递质代谢的影响。方法 应用WHO推荐的神经行为检测组合（NCTB）对92名汽油作业工人和88名对照工人进行神经行为测试,同时用高效液相色谱法－电化学法联检测定其尿中高香草酸（HVA）和香草扁桃酸（VMA）的浓度。结果 接触组明显存在忧郁－沮丧的不良情绪状态,简单反应时慢于对照组,数字跨度、提转捷度、数字译码和目标追中学踪得分明显低于对照组,且行为功能得分随浓度的增高而降低;汽油接触工人尿中HVA和VMA浓度均降低。结论 提示职业性低浓度接触无铅汽油油可影响神经行为功能和单胺类神经递质代谢。     

微波辐射对人体健康影响的调查研究

本文对33名微波作业人员进行了职业危害调查。结果表明:微波组神经衰弱综合征的发生率高于对照组,有极显著差异(P<0.01);血压偏低、心动过缓、晶状体混浊和尿香草扁桃酸(VMA)排出增高的检出率,微波组明显高于对照组(P<0.05)。作者认为尿VMA可能是微波辐射早期影响的客观指标之一。     

丙烯腈对大鼠脑单胺类神经递质及其代谢产物的影响

目的　评价长期低浓度接触丙烯腈对大鼠脑单胺类神经递质及其代谢产物的影响。方法　雄性SD大鼠 30只,随机分成对照组、低剂量组和高剂量组,每组 10只。通过饮水对大鼠进行丙烯腈染毒,分别给予 0、50和 200mg/L的丙烯腈溶液。染毒时间为 12周。染毒结束后从每组随机选取 7只大鼠迅速分离双侧纹状体和小脑皮层,测定单胺类神经递质及其代谢产物的浓度,并取大脑皮层测定单胺氧化酶活性。结果　随着染毒剂量的增加,低剂量组和高剂量组大鼠纹状体中的多巴胺含量分别降低到 (2 .2±0 .7)和 (3 .2±2 .0)μg/g脑湿重,与对照组的多巴胺含量 ( 9. 0±4.2)μg/g脑湿重比较,差异有统计学意义。3组大鼠小脑中的多巴胺未见减少,其代谢产物 3, 4 双羟苯乙酸分别为(186±41)、(245±90)和(115±65)ng/g脑湿重,低剂量组显著升高。3组染毒大鼠纹状体内的 5 羟色胺含量分别为 (249±34)、(155±95)和 (128±101)ng/g脑湿重,呈逐渐下降趋势,并具有显著的剂量 效应关系,但 3组大鼠小脑中的 5- 羟色胺及其代谢产物含量的变化无统计学意义。3组大鼠脑组织纹状体和小脑中的去甲肾上腺素及其代谢产物以及脑皮层单胺氧化酶活性的改变均无统计学意义。结论　丙烯腈对单胺类神经递质及其代谢产物的影响可能是其神经行为毒性的生物学     

全氟辛烷磺酸对大鼠脑组织氨基酸类神经递质和谷氨酰胺合成酶的影响

目的探讨全氟辛烷磺酸(PFOS)与大鼠中枢神经系统兴奋性氨基酸和谷氨酰胺合成酶(GS酶)的剂量反应关系。方法将20只成年雄性Wister大鼠随机分为4组(对照组、4个染毒组)每组5只。大鼠染毒PFOS(12.5、25、50mg/kg)5天后,对照组给予等体积的2%吐温-80溶液,应用高效液相色谱法测定脑组织氨基酸类神经递质及谷氨酰胺合成酶的改变。结果与对照组比较,大鼠自发活动能力下降;50mg/kg体重组海马谷氨酸含量显著降低,25和50mg/kg体重组皮质谷氨酸含量显著降低;随着染毒剂量的增加海马GS酶活性增加,其中12.5mg/kg剂量组和25mg/kg剂量组明显高于对照组(P<0.05)。结论氨基酸类神经递质含量的改变是PFOS神经毒性的机制之一。     

百草枯对小鼠脑组织脂质过氧化及单胺类神经递质含量的影响

目的 观察百草枯对小鼠脑组织中脂质过氧化与单胺类神经递质的影响.方法 40只健康成年昆明种小鼠随机分为高、中、低百草枯染毒组和对照组,每组10只,高、中、低百草枯染毒组的染毒剂量分别是8.00、2.67、0.89mg/kg,对照组为蒸馏水.经口灌胃,1次/d,连续染毒28d后,测定脏器系数,脑组织中超氧化物歧化酶(SOD)活力、丙二醛(MDA)含量以及多巴胺(DA)、去甲肾上腺素(NE)含量.结果 中、高剂量组MDA含量为(1.24±0.70、1.60±0.13)nmol/mg,明显高于对照组的(0.22±0.10)nmol/mg;低、中、高剂量染毒组SOD活力为(5.47±0.19、4.67±0.89、4.23±1.59)u/mg,明显低于对照组的(6.96±0.46)u/mg,差异均有统计学意义(P<0.05或P<0.01).中、高剂量组脑组织中DA含量,高剂量组NE含量均明显低于对照组,差异有统计学意义(P<0.05或P<0.01).中、高剂量组小鼠脑系数及高剂量组肺脏系数明显高于对照组,差异有统计学意义(P<0.05或P<0.01).结论 百草枯导致小鼠脑组织脂质过氧化增强,影响脑内单胺类神经递质的含量,对神经系统具有毒性作用.     

去铁酮对铝染毒大鼠脑组织中甘氨酸和γ-氨基丁酸及铝和必需元素的影响

目的探讨去铁酮(defriprone,DFP)对铝染毒大鼠脑组织中甘氨酸(Gly)、γ-氨基丁酸(GABA)两种抑制性氨基酸类神经递质及铝和必需元素影响。方法将35只健康清洁级Wistar雄性大鼠按体重随机分为5组,分别为阴性对照组和铝单独染毒组以及铝+低、中、高剂量DFP组,每组7只,采用灌胃方式染毒,每天1次,每周连续染毒5 d,间隔2 d。前8周,阴性对照组给予生理盐水(1 ml/d),其他4组给予AlCl3溶液(354.7 mg/kg)。后2周,阴性对照组与铝染毒组给予生理盐水(1 ml/d);铝+DFP低、中、高剂量组分别给予不同浓度DFP溶液(13.72、27.44和54.88 mg/kg),每天1次。测定脑组织中Gly、GABA及铝、铜、镁、钙和铁的含量。结果与阴性对照组比较,铝单独染毒组和铝+各剂量DFP组大鼠脑组织中Gly和GABA的含量均较高,差异有统计学意义(P<0.01)。与铝单独染毒组比较,铝+各剂量DFP组大鼠脑组织中Gly和GABA的含量均较低,差异有统计学意义(P<0.01)。与阴性对照组比较,铝单独染毒组和铝+低、中剂量DFP组大鼠脑组织中铝含量均较高,差异有统计学意义(P<0.01)。与铝单独染毒组比较,铝+各剂量DFP组大鼠脑组织中铝含量均较低,差异有统计学意义(P<0.01);且随着DFP剂量的升高,大鼠脑组织中的铝含量呈下降趋势。各组大鼠脑组织中铜、镁、钙和铁含量间比较,差异均无统计学意义。结论 DFP可通过促进铝排出,恢复铝染毒大鼠脑组织中Gly和GABA的正常代谢,且对铜、镁、钙、铁等必需元素在脑中平衡不产生影响,对中枢神经系统具有明显保护作用。     

铝对神经行为功能和单胺类神经递质代谢的影响

目的评价职业性铝接触对神经行为功能和单胺类神经递质代谢的影响。方法对３３名铝作业工人和４０名对照工人进行研究。作业环境空气铝的测定用原子吸收仪，尿中高香草酸和香草扁桃酸及血清和尿铝的测定用高效液相色谱仪，神经行为功能测试采用ＷＨＯ推荐的神经行为核心测试组合。结果作业环境铝的时间加权几何平均浓度为０．９５ｍｇ／ｍ３（０．３１～４．１２ｍｇ／ｍ３），铝作业工人尿铝平均水平显著高于对照工人（分别为１２．２５μｇ／Ｌ和５．７８μｇ／Ｌ），但血清铝水平与对照工人差异未见显著性；铝作业工人尿中的高香草酸和香草扁桃酸水平均较高，且香草扁桃酸水平显著高于对照工人；神经行为功能测试发现，接触工人的手提转捷度、数字译码和视觉保留测试项目得分与对照工人比较差异有显著性。结论提示职业性低浓度接触铝可影响神经行为功能和单胺类神经递质代谢。     

铝熔铸作业工人神经行为功能的研究

为探讨铝对作业工人神经系统的影响，寻找对铝作业工人健康监护的早期指标，对３６名铝熔铸作业工人（车间空气中铝尘和铝浓度分别为１．６５ｍｇ／ｍ３和０．２５ｍｇ／ｍ３（ＴＷＡ））和４０名对照工人，应用ＷＨＯ－ＮＣＴＢ进行了神经行为功能测定；同时测定了尿铝、尿中高香草酸（ＨＶＡ）和香草扁桃酸（ＶＭＡ）的含量。结果发现：铝接触工人注意力、手的运动协调能力、视感知记忆力下降，反应时的标准差和最慢反应时间延长（Ｐ＝０．００２５，Ｐ＝０．００６６），提转捷度测试得分降低（Ｐ＝０．０２６），数字译码和Ｂｅｎ－ｔｏｎ视觉保留测试得分降低（Ｐ＝０．０２３，Ｐ＝０．００３）。分层分析发现：后３项分测试得分随接触时间延长而降低，铝作业工人尿ＶＭＡ和尿铝含量高于对照组。提示：铝可能对作业工人的神经系统产生影响。神经行为测试和尿ＶＭＡ测定可用于检测铝的不良效应     

The effects of exposure to aluminium on neurobehavioural function and dopaminergic metabolism

A study was conducted to evaluate the effects of exposure to aluminium (Al) on neurobehavioural function and dopaminergic metabolism among 33 exposed workers compared to 40 controls. The parameters measured included concentrations of Al in air, serum Al and urine Al. WHO Neurobehavioural Core Test Battery was used to measure the neurobehavioural functions. Homovanillic acid (HVA) and vanillymandellic acid (VMA), two end products of catecholamine metabolism were measured using high-pressure liquid chromatography (HPLC). Determinations of Al in serum and urine were carried out using precolumn lumogallion reaction HPLC technique. The geometric mean of the airborne concentration of inhalable Al dust was 1.90 mg/m3 (range 0.62-8.24 mg/m³). The mean concentration of Al in urine was significantly higher in the exposed workers than the controls (12.25 ± 6.04 vs 5.78 ± 3.10 ug/l), but no statistical difference was observed for serum Al (1.68 ± 0.63 vs 1.31 ± 0.40 mug/l); suggesting that urinary Al is a better biomarker for Al exposure. The neurobehavioural evaluation showed that there were significant differences for Santa Ana tests, digit symbol and Benton test, implying that the manual dexterity, eye-hand coordination and memory were poorer in the Al-exposed workers. The data also showed that both of the catecholamine metabolites were higher in the exposed group, especially urinary VMA (p < 0.01). These data reflect that exposure to Al could interfere with the dopaminergic metabolism and neurocognitive function.     

Neurochemical effect of lead exposure: a study on catecholamine metabolism

In an attempt to examine the neurochemical changes of lead exposure, a study was conducted on 106 lead workers and a control group of 25 nonexposed workers. The urinary excretion of major catecholamine metabolites, homovanillic acid (HVA), and vanillylmandellic acid (VMA) were measured. Workers exposed to lead had a mean blood lead concentration of 43.2 micrograms/100 ml, whereas the concentration for workers not exposed to lead was 12.7 micrograms/100 ml. Urinary HVA was significantly elevated in the exposed group when compared with controls (p less than 0.01). HVA was also found to be associated with an increase of lead in blood. Although not statistically significant, the VMA excretion was also noted to be moderately elevated; however, it is recognized that the present study was unable to establish a highly significant dose-response relationship between lead exposure and HVA excretion, as has been reported earlier in lead-poisoned children.     

Bacterial contamination of infant urine samples obtained from filter papers used in neuroblastoma-screening tests. (6) Protective effects of preaddition of chlorhexidine digluconate in filter papers or containers for urine on bacterial break-down of creatinine, vanillylmandelic acid and homovanillic acid]

The effects of chlorhexidine digluconate preadded to urine samples for a neuroblastoma-screening test in preventing the break-down of creatinine (Cre), vanillylmandelic acid (VMA), and homovanillic acid (HVA) by creatinine-cleaving bacteria and the influence of the added disinfectant on the HPLC determination of urinary Cre, VMA, vanillillactic acid (VLA) and HVA. Laboratory or field experiments showed that preadded disinfectant (0.02% volume) nearly completely inhibited the growth of the bacteria and satisfactorily protected urinary Cre, VMA, and HVA from bacterial decomposition. Chlorhexidine digluconate was comparable to benzalkonium chloride in its inhibitory effects on the growth and activities of creatinine-cleaving bacteria. Unlike benzalkonium chloride, chlorhexidine digluconate added to urine samples gave no troubles in subsequent analytical processes. Addition of the disinfectant (0.02% volume) to standard Cre, VMA, VLA, and HVA solution did not affect retention times and sensitivities in HPLC analyses. To estimate influences of the added disinfectant on the serial HPLC determinations of VMA, VLA, and HVA on a large number of urine samples (40, 80, 120, 160, 200, or 5, 500), HPLC analyses were performed on standard VMA, VLA, and HVA solution with repeated injection of the disinfectant in great amounts into a column. The results showed no appreciable changes in the retention times and sensitivities of VMA, VLA, and HVA, and almost complete elution of the disinfectant retained on the column were possible with water-methanol (1:1, 2:8) or methanol washing.(ABSTRACT TRUNCATED AT 250 WORDS)     

莱菔硫烷对汞致大鼠肾急性损伤的保护作用

目的 探讨莱菔硫烷(sulforaphane,SFN)对莱菔硫烷(sulforaphane,SFN)所致大鼠急性肾损伤的保护作用。 方法 清洁级Wistar大鼠30只按体重随机分5组,每组6只,分别为对照组,低、中、高剂量染汞组, SFN干预组。对照组及各染汞组皮下注射生理盐水,SFN干预组皮下注射2 mg/kg SFN;2 h后,对照组腹腔注射生理盐水,其他四组腹腔注射2.2、4.4、8.8、8.8 μmol/kg HgCl₂,连续3 d,染毒容量均为5 ml/kg。于最后一次染毒结束后,测定尿液中Hg及尿蛋白含量,碱性磷酸酶(ALP)、乳酸脱氢酶(LDH)和β-N-乙酰氨基葡萄糖苷酶(NAG)活力;腹主动脉采血测定血清尿素氮(BUN)含量;测定肾皮质中Hg含量和谷胱甘肽(GSH)、丙二醛(MDA)水平及超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)活力。分析各组各项指标差异。 结果 与对照组比较,各剂量染汞组大鼠尿Hg、肾皮质Hg含量,尿蛋白和血清BUN 含量,尿NAG、LDH 和ALP 活力,肾皮质中GSH 和MDA含量显著升高(P<0.05或P<0.01);肾皮质SOD 和GSH-Px 活力显著降低(P<0.05或P<0.01)。与8.8 μmol/kg HgCl₂组比较,SFN 干预组尿蛋白和血清BUN 含量、尿NAG、LDH 和ALP活力、肾皮质GSH 、MDA含量均显著下降(P<0.05或P<0.01);肾皮质SOD 和GSH-Px 活力显著升高(P<0.01),而尿汞、肾皮质汞含量间差异无统计学意义(P>0.05)。 结论 莱菔硫烷对汞所致大鼠急性肾毒性有一定的保护作用。     

Effects of occupational exposure to polychlorinated biphenyls on urinary metabolites of neurotransmitters: A cross-sectional and longitudinal perspective

BackgroundPolychlorinated biphenyls (PCBs) are chemicals which were used for industrial purposes and are known to induce various adverse health effects. They are also known to be neurotoxic and numerous targets within the central nervous system have been identified in previous studies. Specifically, the neurotransmitters dopamine (DA) and norepinephrine (NE) are influenced by PCBs as indicated in studies involving animals. However, limited evidence has been published documenting PCB induced changes in the neurotransmitter system in humans.ObjectiveIn the present study, we examined the association between a higher PCB body burden following occupational exposure and possible changes in human neurotransmitter metabolites.MethodsWithin a medical surveillance programme called HELPcB (Health Effects in High-Level Exposure to PCB) that monitors adverse health effects of occupational PCB exposure, urine samples were obtained (n_T1 = 166; n_T2 = 177 and n_T3 = 141). The urinary concentrations of the metabolites homovanillic acid (HVA; for DA) and vanillylmandelic acid (VMA; for NE) were analyzed. Blood samples were obtained by vena puncture in order to determine the internal exposure to PCBs with human biomonitoring.ResultsA cross-sectional analysis indicated a significant negative effect of PCB exposure on HVA and VMA. Longitudinally, an initially higher exposure to higher chlorinated PCBs was followed by constant reduced HVA level over three consecutive years. Exploratory analyses show different long-term effects for different PCBs according to their chlorination degree. A higher exposure with lower chlorinated PCBs leads to an increase of VMA and HVA. Conversely, a higher exposure to all PCBs results in a reduction of HVA.ConclusionThis study, to our knowledge, is the first to document changes in neurotransmitter metabolites after occupational PCB exposure in humans. This finding advances evidence obtained from past research, and identifies one potential pathomechanism in the central dopaminergic system of humans.     

Analysis of urinary porphyrins in rats exposed to aluminum and iron

The mechanism by which excess aluminum induces anemia may be aluminum overload resulting from a reversible block in heme synthesis due either to a defect in porphyrin synthesis or to impaired iron utilization. Studies were conducted to define the specific changes in the urinary porphyrin excretion pattern (porphyrin profile) and the time course of those changes in rats exposed to aluminum. In these studies, aluminum chloride (AlCl3) was orally administered to female Wistar rats at the dose of 100 mg Al/kg for 35 days with or without FeCl2 (4 mg Fe/kg). Control rats were treated with 0.9% NaCl or with FeCl2 (4 mg/kg). The dynamics of urine porphyrins (8-, 7-, 6-, 5-, and 4-carboxyporphyrins) was determined by HPLC on the 7th, 14th, 21st, 28th, and 35th days in both exposed and control groups of rats. The results of the experiment indicate that aluminum induced a statistically significant increase in the percentage of uroporphyrin and a decrease in coproporphyrin in urine (cumulative dose, 2100 mg Al/kg). Changes in urinary porphyrins were observed when the concentration of aluminum in serum was at 48 microg Al/L on average. Administration of iron together with aluminum diminished the described changes in porphyrins metabolism caused by aluminum itself.