哺乳期母鼠镧暴露对子代脑组织氧化损伤影响

目的 探讨哺乳期镧暴露对子代大鼠脑组织氧化损伤的影响.方法 Wistar大鼠交配产子后,通过自由饮水方式对各组大鼠进行处理,其中对照组饮用蒸馏水;低剂量组饮用含0.25%三氯化镧(LaCl<,3>)蒸馏水溶液;中剂量组饮用含0.5%LaCl<,3>蒸馏水溶液;高剂量组饮用含1.0%LaCl<,3>蒸馏水溶液,连续染毒至仔鼠断乳,测量仔鼠体重、脑组织重量并计算脑组织系数,取仔鼠脑组织测量丙二醛(MDA)、还原型谷胱甘肽(GSH)、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)含量.结果 与对照组比较,仔鼠体重、脑组织重量均呈下降趋势,对照组、低剂量组、中剂量组、高剂量组MDA值分别为60.51,68.90,80.26,90.65 nmol/(mg pro);GSH值分别为16.78,14.99,11.58,11.15 mg/(g pm);SOD值分别为40.55,35.66,36.61,32.01U/(mg pro);GSH-Px值分别为2.07,2.93,0.94,0.58U/(mg pro).结论 哺乳期镧暴露可使子代大鼠脑组织中的抗氧化物质GSH减少,抗氧化酶SOD和GSH-Px活性降低,发生脂质过氧化.     

牛黄酸和VC对染砷小鼠脑神经损伤保护作用

目的观察牛黄酸和维生素C（VC）对砷暴露导致的脑组织核酸损伤的保护作用，为砷毒性脑损伤的预防和治疗提供科学依据。方法昆明种小鼠40只，随机分为4组：4mg／L三氧化二砷染毒组、150mg／kg牛黄酸和45mg／kgVC拮抗组以及生理盐水对照组。每周2次，连续染毒60d，取小鼠脑组织固定，用免疫组化方法观察脑组织神经细胞8-硝基鸟嘌呤（8-NO2-G）的表达。结果染砷组小鼠脑组织出现异常病理学改变，脑皮质神经细胞的胞浆中8-NO2-G呈现明显的高表达。而牛黄酸和VC拮抗组小鼠脑组织出现轻度的病理学变化8-NO2-G表达。结论牛黄酸和VC对砷暴露小鼠脑组织RNA损伤具有保护作用。     

外源性谷胱甘肽对饮水砷暴露雌性小鼠脑砷形态及一氧化氮代谢的影响

目的 探讨外源性谷胱甘肽(glutathione,GSH)对饮水砷暴露小鼠脑中砷形态分布及一氧化氮(nitric oxide,NO)代谢的影响.方法 将40只雌性昆明小鼠随机分为对照组、单独染砷(NaAsO_2)组及低剂量(200mg/kg)、中剂量(400mg/kg)或高剂量(800mg/kg)GSH干预组,每组8只.染毒组小鼠饮水染砷4周,在最后一周,在染砷同时腹腔注射不同剂量GSH.末次注射后24h处死小鼠,取血和脑组织,分别检测无机砷(iAs)、一甲基胂酸(MMA)和二甲基胂酸(DMA)含量及脑中一氧化氮合酶(NOS)活力和NO含量.结果 GSH干预组小鼠血中iAs、MMA和总砷(TAs)含量及脑中DMA和TAs含量与单独染砷组比较显著下降.与对照组相比,单独染砷组小鼠脑中NOS活力及NO含量显著降低.与单独染砷组比较,中、高剂量GSH干预组小鼠脑中NOS活力显著升高.结论 给予外源性GSH可减少血液和脑组织中的砷负荷,进而改善砷对脑内NO代谢的影响.     

CYP2E1在1,2-二氯乙烷致脑氧化损伤中的作用

分别将昆明种小鼠随机分为对照组、单纯染毒组及低、中和高剂量二烯丙基硫化物(DAS)干预组。检测脑组织中CYP2E1蛋白和mRNA表达、MDA和GSH含量及SOD活性。单纯染毒组与对照组相比,小鼠脑组织中CYP2E1蛋白和mRNA表达及MDA含量显著升高,而GSH含量显著下降;DAS各干预组与单纯染毒组相比,CYP2E1蛋白和mRNA表达及MDA含量显著下降,GSH含量显著升高。提示1,2-DCE可诱导CYP2E1表达,导致脑组织氧化损伤。     

砷对仔代大鼠脑组织氧化损伤及超微病理结构的影响

目的观察砷对仔代大鼠生长发育不同时期脑组织氧化应激状态影响和脑组织病理学变化,探讨砷致脑损伤的机制。方法雌性大鼠于受孕后第6天开始以自由饮水方式分别暴露10、50和100 mg/L的NaAsO2水溶液,连续染毒直到仔鼠出生后第42天,分别于仔鼠出生后第12小时、第28天、第42天处死仔鼠,取大脑皮质、海马结构进行氧化性指标测定,并在第42天观察仔鼠大脑皮质病理形态学变化。结果仔鼠出生后第12小时,100 mg/L砷染毒组脑组织中丙二醛(MDA)含量〔(7.23±2.32)nmol/(mg.Pr)〕明显高于对照组〔(4.58±0.95)nmol/(mg.Pr)〕,出生后第28天、第42天,100 mg/L砷染毒组大脑皮质MDA含量明显升高,而海马结构中MDA在各组间比较,差异无显著性。脑中抗氧化物质谷胱甘肽(GSH)含量在仔鼠出生后第12小时、第28天,各砷染毒组均未发生显著改变,但在出生后第42天100 mg/L砷染毒组仔鼠大脑皮质〔(21.57±12.55)mg/(g.Pr)〕、海马结构〔(21.55±10.59)mg/(g.Pr)〕中GSH含量均明显低于对照组〔(36.20±4.59)mg/(g.Pr)〕、〔(39.38±20.65)mg/(g.Pr)〕,并且抗氧化酶谷胱甘肽过氧化酶(GSH-Px)活力也呈明显降低趋势。脑组织的透射电镜观察显示50 mg/L砷染毒组仔鼠脑组织神经元呈空泡变,核染色质聚积于核膜下,核肿胀,呈水样变性。100 mg/L砷染毒组仔鼠脑组织神经元内质网极度扩张,游离核糖体消失。结论砷可以通过胎盘屏障进入仔鼠体内,并可透过血脑屏障引起脑组织脂质过氧化,从而破坏脑组织生物膜结构引起一系列生理病理改变。     

砷暴露对不同发育阶段仔鼠海马SR水平的影响

建立不同发育阶段仔鼠砷暴露模型,记录体重,采用水迷宫检测砷暴露对仔鼠学习记忆能力的影响,取脑组织并分离海马,采用Real-time RT-PCR检测SR mRNA水平。结果显示,仔鼠出生后(PND)20天,60 mg/L NaAsO_2组仔鼠体重显著低于对照组和15 mg/L NaAsO_2组;PND 40时30和60 mg/L NaAsO_2组仔鼠体重显著低于对照组,60 mg/L NaAsO_2组仔鼠体重显著低于15和30 mg/L NaAsO_2组;水迷宫实验训练第5天,不同剂量砷暴露组仔鼠寻找平台的潜伏期均显著高于对照组;60 mg/L NaAsO_2组仔鼠在撤台后第Ⅱ象限停留时间显著低于对照组;PND20时,60 mg/L NaAsO_2组SR mRNA水平明显低于对照组,PND 40时30和60 mg/L NaAsO_2组仔鼠SR mRNA水平均显著低于对照组。提示砷暴露可使仔鼠海马SR的水平降低,从而影响学习记忆能力。     

妊娠期至性成熟期饮水砷暴露对子代小鼠海马组织中DNA甲基转移酶mRNA表达的影响

目的研究妊娠期至性成熟期砷暴露致子代小鼠海马DNA甲基转移酶(DNA methyltransferase,DNMTs)水平的影响,探讨不同浓度砷暴露导致子代小鼠学习与记忆能力损伤的相关分子机制。方法将24只妊娠第1天的SPF级小鼠随机分为对照组、15、30和60 mg/L亚砷酸钠染毒组,仔鼠断乳之前经母鼠染砷,断乳至出生后(postnatal day,PND)40天以自行饮水方式进行砷暴露。对PND40子代小鼠进行水迷宫检测,PND10、PND20和PND40仔鼠取脑并分离海马,采用实时荧光定量RT-PCR(Real-time RT-PCR)法测定子代小鼠海马DNMT1、DNMT3a和DNMT3b mRNA水平。结果水迷宫结果显示,从训练第4天开始,不同浓度砷暴露组仔鼠寻找平台潜伏期均明显长于对照组,差异具有统计学意义(P0.05);在撤平台后,30和60 mg/L亚砷酸钠染毒组与对照组相比,仔鼠在第Ⅱ象限停留时间明显缩短,差异具有统计学意义(P0.05);30和60 mg/L亚砷酸钠染毒组PND20仔鼠海马DNMT1 mRNA的表达水平明显高于对照组,差异具有统计学意义(P0.05);PND10和PND40各组仔鼠海马DNMT1 mRNA的表达水平均无统计学差异(P0.05)。不同发育阶段各组仔鼠海马DNMT3a和DNMT3b mRNA的表达水平均无统计学差异(P0.05)。结论砷暴露损伤仔鼠学习记忆能力可能与海马DNMT1 mRNA水平升高有关。     

抗坏血酸对染砷小鼠肝脏氧化损伤拮抗作用

目的 研究抗坏血酸(VC)对砷中毒小鼠肝脏中丙二醛(MDA)、超氧化物歧化酶(SOD)和谷胱甘肽(GSH)的影响.方法 用硫代巴比妥酸法测定丙二醛(MDA)含量;用Nitrite-kit法检测SOD活性;用二硫双硝基苯酸(DTNB)比色法测定GSH含量.结果 对照组MDA含量为14.87 nmol/(mg·prot),SOD活力为167.49NU/(mg·prot),GSH含量为51.27 nmol/(mg·prot);20 μmol/L染砷组小鼠肝脏中MDS含量明显增高,为18.48nmol/(mg·prot),SOD活力明显下降,为125.97 NU/(mg·prot),GSH含量也显著降低,为34.87 nmol/(mg·prot);而抗坏血酸拮抗组小鼠肝脏中MDS含量与单纯染砷组相比明显下降,为16.24 nmol/(mg·prot),但未达到对照组水平;SOD活力明显增高,为138.94 NU/(mg·prot),但未达到对照组水平,GSH含量显著增高,为50.39 nmol/(mg·prot),与对照组比较差异无统计学意义.结论 抗坏血酸可拮抗砷对小鼠肝脏的氧化损伤.     

外源性谷胱甘肽对慢性砷暴露小鼠尿砷代谢及氧化应激的影响

目的探讨给与谷胱甘肽(GSH)及其拮抗剂——丁硫氨酸亚砜胺(BSO)对慢性砷暴露小鼠体内砷代谢及氧化应激的影响。方法将SPF级雌性昆明小鼠随机分为对照组(蒸馏水)、单纯染砷组(50 mg/L亚砷酸钠)、GSH干预组(50 mg/L亚砷酸钠+400 mg/kg GSH)和BSO(50 mg/L亚砷酸钠+600mg/kg BSO)干预组,除对照组小鼠饮用蒸馏水外,其余各组均饮用含50 mg/L亚砷酸钠的水溶液连续染毒30周,然后给予400 mg/kg GSH或600 mg/kg BSO,用蒸馏水配制GSH和BSO水溶液,每天两次腹腔注射,连续2 d,用氢化物发生-超低温捕集-原子吸收分光光度法测定尿液各形态砷水平,用DTNB及试剂盒法分别测定全血及肝脏中GSH和总抗氧化能力(T-AOC)水平。结果 GSH干预组小鼠尿中二甲基胂(DMA)、DMA含量构成比、二甲基化率(SMR)及总砷含量高于单纯染砷组(P<0.05),而BSO干预组各形态砷、DMA含量构成比、一甲基化率(FMR)、SMR及总砷含量均低于单纯染砷组(P<0.05);单纯染砷组小鼠肝脏和血液GSH和T-AOC的水平均低于对照组(P<0.05)。给予GSH干预后,肝脏和血液GSH和T-AOC水平均高于单纯染砷组(P<0.05)且与对照组差异无统计学意义(P>0.05)。BSO干预组小鼠肝脏和血液GSH和T-AOC的水平均低于其他各组(P<0.05)。结论外源性GSH干预可以增强砷暴露小鼠的砷甲基化能力,增加砷从尿液中的排出,拮抗砷所致的GSH和T-AOC水平下降,从而减少了砷对机体造成的氧化损伤。     

胚胎期和生长期大鼠砷暴露对仔鼠体重和脑神经递质的影响

为研究砷对大鼠脑组织氨基酸神经递质水平的影响并探讨砷的脑损伤机制,将SD大鼠(雄雌各半)随机分为对照组(A组)、子代染砷组(B组)、母子染砷组(C组)。A、B组饮蒸馏水,C组饮As2O3水溶液[50mg/L,相当于10mg/(kg·d)],6周时,各组雌雄分别2:1合笼产仔,仔鼠乳养至断乳,仔鼠继续按本组剂量染砷到断乳后第12周。测定仔鼠的大脑皮质氨基酸(天冬氨酸、谷氨酸、赖氨酸、甘氨酸、γ-氨基丁酸、精氨酸、丙氨酸、组氨酸)水平。各组仔鼠分别于断乳后染砷0、4、12和24周时称取体重。结果显示,砷暴露12周的B组和C组的仔鼠大脑皮层谷氨酸和天冬氨酸水平均高于对照组,以C组的仔鼠谷氨酸升高更明显,差异有统计学意义(P0.01),r-氨基丁酸、甘氨酸等与对照组比较无显著差异。B组雄性仔鼠染砷4和12周时的体重增长均高于对照组(P0.01),而24周时B组的雄性仔鼠体重增长则明显低于对照组(P0.01);B组雌性仔鼠前4周体重增长高于对照组(P0.01),12周和24周时体重增长则明显低于对照组;C组的雄、雌仔鼠体重增长均低于对照组和B组的雄、雌仔鼠(P0.01)。本研究的砷暴露剂量能致子代大鼠大脑皮层谷氨酸水平升高,以母代染砷的仔鼠升高更显著。砷暴露初期有促进大鼠体重增长效应,长期砷暴露对体重增长幅度有抑制作用,以母代染砷的仔鼠更显著且雌性仔鼠更敏感。     

Allergy and occupational exposure to hydroquinone and to methionine

Respiratory manifestations have been reported after exposure to hydroquinone and to methionine. One hundred and three men in the same chemical plant were divided into three groups according to their exposure and compared by questionnaire, respiratory functional tests with methacholine then salbutamol challenges, and measurements of serum immunoglobulins G and E. Group H included 33 workers exposed to hydroquinone, trimethyl-hydroquinone, and retinene-hydroquinone. Group M included 15 workers exposed to methionine. Group C was a control group of 55 workers. The prevalence of respiratory symptoms was higher in the two exposed groups. Before challenges, pulmonary function values were significantly lower in groups H and M than those in group C. The challenges induced significant variations in the three groups but these variations were less pronounced in group M than in the other groups. The level of immunoglobulin G in group H (m +/- SD = 12.5 gram/liter +/- 2.6) was significantly higher than in group C (10.6 gram/liter +/- 2.4; p less than 0.002). The level of immunoglobulin E in group H (m = 140 IU/l) was also higher in group C (109 IU/l) but this difference was not significant. These findings suggest that exposure to methionine and to hydroquinone and its derivatives induce ventilatory impairment, perhaps by an immunological mechanism.     

Ototoxic effects of occupational exposure to styrene and co-exposure to styrene and noise

Ototoxicity of styrene and the synergistic action of styrene and noise have been shown in rats. The respective data in humans are scarce and equivocal. This study evaluated the effects of occupational exposure to styrene and combined exposures to styrene and noise on hearing. The study group, comprised of 290-yacht yard and plastic factory workers, was exposed to a mixture of organic solvents, having styrene as its main compound. The reference group, totaling 223 subjects, included (1) white-collar workers, exposed neither to solvents nor noise and (2) metal factory workers, exposed exclusively to noise. All subjects were assessed by means of a detailed questionnaire and underwent otorhinolaryngological and audiometric examinations. Multiple logistic regression analysis revealed almost a 4-fold (or 3.9; 95% CI = 2.4-6.2) increase in the odds of developing hearing loss related to styrene exposure. The factors adjusted for were: age, gender, current occupational exposure to noise, and exposure to noise in the past. In cases of the combined exposures to styrene and noise, the odds ratios were two to three times higher than the respective values for styrene-only and noise-only exposed subjects. The mean hearing thresholds--adjusted for age, gender, and exposure to noise--were significantly higher in the solvent-exposed group than in the unexposed reference group at all frequencies tested. A positive linear relationship existed between an averaged working life exposure to styrene concentration and a hearing threshold at the frequencies of 6 and 8 kHz. This study provides the epidemiological evidence that occupational exposure to styrene is related to an increased risk of hearing loss. Combined exposures to noise and styrene seem to be more ototoxic than exposure to noise alone.     

Effects of occupational exposure to estrogen and progestogens and how to detect them

This report describes the health effects of occupational exposure during manufacturing processes that utilize synthetic estrogens and progestogens, and demonstrates the usefulness of various laboratory assays in identifying workers who have experienced actual hormone absorption. In late 1978 the health status of exposed and unexposed workers was compared by standardized questionnaire, physical examination, and laboratory studies. A higher proportion of exposed than unexposed men gave histories of breast swelling (p less than .0001), nodules (p = .0003), and nipple discharge (p = .037). Physical examination showed no significant differences between groups. Exposed and unexposed workers showed no clinically significant differences on any routine laboratory studies. Hormone studies revealed significantly lower natural total serum estrogen levels in exposed men and women. Serum norethindrone levels were useful in identifying workers with hormone exposure in their recent past. Hormone exposure continued to cause physiologic disturbances during the period studied despite efforts to control exposure. Measuring blood norethindrone levels may be a valuable way of identifying exposed workers.     

Allergy and occupational exposure to hydroquinone and to methionine.

Respiratory manifestations have been reported after exposure to hydroquinone and to methionine. One hundred and three men in the same chemical plant were divided into three groups according to their exposure and compared by questionnaire, respiratory functional tests with methacholine then salbutamol challenges, and measurements of serum immunoglobulins G and E. Group H included 33 workers exposed to hydroquinone, trimethyl-hydroquinone, and retinene-hydroquinone. Group M included 15 workers exposed to methionine. Group C was a control group of 55 workers. The prevalence of respiratory symptoms was higher in the two exposed groups. Before challenges, pulmonary function values were significantly lower in groups H and M than those in group C. The challenges induced significant variations in the three groups but these variations were less pronounced in group M than in the other groups. The level of immunoglobulin G in group H (m +/- SD = 12.5 gram/liter +/- 2.6) was significantly higher than in group C (10.6 gram/liter +/- 2.4; p less than 0.002). The level of immunoglobulin E in group H (m = 140 IU/l) was also higher in group C (109 IU/l) but this difference was not significant. These findings suggest that exposure to methionine and to hydroquinone and its derivatives induce ventilatory impairment, perhaps by an immunological mechanism.