母鼠孕前营养过剩对子代小鼠生长发育影响

目的构建孕前营养过剩及超重小鼠模型,探讨孕前营养过剩对子代小鼠生长发育影响。方法 20只昆明种雌鼠随机分为对照组和实验组,分别给予标准饲料和高脂高糖饲料;两组单纯饲养4周后与雄鼠合笼,孕期继续上述饮食;产后均母乳喂养,产后3w断乳,哺乳期间母鼠仍按各自组别进食;监测单纯饲养期、孕期和哺乳期母鼠体重、血糖变化。两组子鼠断乳后一律以标准饲料喂养,监测子鼠出生至生后5w体重、身长和尾长发育。结果 1.母鼠体重和血糖变化：单纯饲养1周后开始实验组母鼠体重持续显著高于对照组（P〈0.05）;饲养1w和4w时,实验组母鼠血糖显著高于对照组（P〈0.05）。孕中、晚期实验组母鼠体重与对照组无显著差异（P〉0.05）。哺乳期两组母鼠体重、血糖均无显著差异（P〉0.05）。2.母乳喂养期子鼠发育：出生3天和7天,实验组子鼠体重显著高于对照组（P〈0.05）;整个母乳喂养期,实验组子鼠尾长显著长于对照组（P〈0.05）,两组子鼠身长无显著差异（P〉0.05）。3.自由采食期子鼠发育：整个自由采食期,实验组雌性子鼠体重显著高于对照组（P〈0.05）;出生35天,实验组雄性子鼠体重也显著高于对照组（P〈0.05）;整个自由采食期,实验组子鼠尾长均显著长于对照组（P〈0.05）,两组子鼠身长无显著差异（P〉0.05）。结论通过高脂高糖饲料可以建立孕前营养过剩及超重小鼠模型,母鼠孕前营养过剩导致子代小鼠出生体重增加以及成年早期肥胖,其对机体的深入影响及机制值得进一步研究。     

PSD-95参与大鼠孕期铅暴露对子代海马突触影响的实验研究

目的:研究大鼠孕期铅暴露后子代海马突触变化与PSD-95表达改变的相关性,探讨铅暴露损伤学习记忆功能的机制。方法:通过饮用0.02%醋酸铅水溶液建立孕期铅暴露模型,利用原子吸收分光光度仪检测血铅,透射电镜技术检测海马突触密度,蛋白印记技术检测子代大鼠海马组织中VGLUT、VGAT和PSD-95的表达。结果:对照组和铅暴露组雄性21 d大鼠体重分别为(55.73±4.23)g和(56.01±5.97)g,无显著差异(P0.05);对照组与铅暴露组雄性21 d大鼠血铅分别为(10.2±2.1)μg/L和(301.2±34.8)μg/L,血铅水平明显升高(P0.01);对照组与铅暴露组雄性21 d大鼠单位面积突触数目分别为32.79±2.03和23.46±1.97,突触密度明显减少(P0.01);铅暴露后,VGAT的表达量没有明显变化(P0.05),VGLUT和PSD-95的表达量明显减少(P0.01)。结论:PSD-95表达减少引起海马兴奋性突触数目的下降是发育期铅暴露损伤学习记忆功能的可能机制。     

珠海地区胎儿铅暴露状况及其影响因素的探讨

目的:了解珠海市人群的胎儿铅暴露水平及其影响因素。方法:在珠海市收集脐带血标本81份,用电感耦合高频等离子体发射光谱仪测定血铅浓度,并以面谈问卷的形式对相应的81名产妇进行了社会环境及家庭生活因素调查。结果:81例脐带血血铅水平呈正态分布,范围在0590μg/L。平均值为150μg/L。脐带血血铅水平超过目前认为的安全界限(100μg/L)占67.9%。研究还发现孕妇居住房屋年代、孕妇居住地、孕期食用罐头食品是胎儿铅暴露的危险因素。多元Logistic回归分析发现,食用罐头食品对脐血铅水平的贡献在考虑了其他掺杂因素的影响后仍有统计学意义。结论:目前珠海市环境铅污染状况可能对胎儿的发育产生不利影响。     

铅暴露对大鼠学习和记忆的影响

目的:研究低水平铅暴露对大鼠学习和记忆的影响。方法:0.05%水平醋酸铅污染大鼠饮用水28天,用Morris水迷宫试验测定大鼠的学习记忆功能。结果:在定位导航任务两组之间没有差异(P>0.05);在探索试验和工作记忆任务中,铅暴露组和正常对照组大鼠成绩显著差异(P<0.01)。结论:铅暴露对大鼠空间参考记忆和工作记忆有明显损害作用,对空间学习未见明显影响。     

孕期及哺乳期铅暴露对大鼠海马神经元树突棘的影响

目的:研究孕期铅暴露对子代大鼠学习记忆功能的影响及其可能的分子机制。方法:通过饮用0.02%醋酸铅水溶液建立大鼠孕期染铅模型,正常饮水为对照组,21 d新生鼠为研究对象,各组12只。检测血铅,利用Morris水迷宫分析系统检测大鼠的学习记忆能力,通过高尔基(Golgi)染色方法观察海马CA1及DG区神经元树突棘的形态和数量的变化。结果:铅暴露组P21新生鼠血铅为31.75±4.83μg/dl,显著高于对照组P21新生鼠(0.96±0.17μg/dl,P<0.01);铅暴露组子代大鼠在定位航行实验中的上台潜伏期较对照组显著延长(P<0.05),在空间探索实验中的目标象限停留时间也较对照组显著降低(P<0.01);CA1区锥体细胞和DG区颗粒细胞的树突棘以蘑菇型和细长型树突棘为主,铅暴露后树突棘主要以粗短型为主。铅暴露组子代CA1和DG去树突棘的密度显著低于对照组(P<0.01)。结论:孕期铅暴露对子代学习记忆功能的影响可能与海马区神经元树突棘的形态变化和密度降低有关。     

孕期低水平铅暴露对新生儿血清磷钙、25(OH)D3及BALP的影响

目的研究孕期低水平铅暴露对新生儿血清磷钙P、Ca、25(OH)D3及骨碱性磷酸酶(BALP)的影响。方法于新生儿娩出断脐后采集脐静脉血5ml分别检测血铅、血清磷钙、血清25(OH)D3及骨碱性磷酸酶,将新生儿以血铅值P50 64.32为界分为低铅组、高铅组,研究脐血铅对新生儿骨代谢相关指标的影响。结果新生儿脐血铅水平与其血清磷、钙和25(OH)D3负相关,与骨碱性磷酸酶水平呈正相关。高铅组与低铅组比较,血清25(OH)D3水平、血清钙几何均数水平显著降低;高铅组碱性磷酸酶水平显著高于低铅组。讨论孕期低水平铅暴露可能干扰了新生儿骨代谢。     

孕前半年父亲铅暴露与子代先天性心脏病病因的关联

目的探讨孕前半年父亲环境危险因素暴露与子代先天性心脏病的病因学关联,为CHD的预防提供依据。方法采用统一制定的调查表,按1:2进行匹配,对先心病例组和对照组的父母分别进行面对面结构式访谈,调查相关的影响因素。结果孕前半年父亲铅暴露(OR=4.516)、母亲自然流产史(OR=5.656)、孕前和孕早期夫妻经常争吵(OR=3.557)与子代CHD的发生存在显著相关性(P0.05)。结论父亲的职业环境和母亲的精神因素应给予高度关注,积极寻找自然流产史夫妇的高危因素,对预防子代CHD的发生尤为重要。     

母体慢性铝暴露对子代鼠海马LTP的损害作用

目的探讨母体于孕前、孕期和哺乳期不同浓度的铝暴露对子代大鼠海马CA3-CA1通路诱导的LTP的影响。方法从孕前30d始至子代断乳止,对照组饮用蒸馏水,低剂量(0.2%Al)和高剂量(0.4%Al)暴露组的母代大鼠分别和铝离子(Al3+)浓度为0.074mol·L-1(2g·L-1)、0.148mol·L-1(4g·L-1)的三氯化铝(AlCl3)蒸馏水溶液;采用石墨炉原子吸收法测定子代鼠的脑铝及血铝含量;采用细胞内记录方法测定子代鼠海马CA3-CA1通路诱导的LTP。结果两暴露组大鼠的血铝和脑铝平均含量明显高于对照组(P<0.05及P<0.01);高频刺激后,两暴露组群体锋电位(PS)幅值增强率(相对于基线值的百分数)逐渐减小,与对照组相比差异非常显著(P<0.01),但两铝暴露组之间差异不显著。结论母体不同浓度的慢性铝暴露可使PS幅值增强率减小,提示铝暴露损害了子代大鼠LTP的诱导与维持。     

脑发育不同阶段慢性铅暴露对大鼠在体海马不同时间一氧化氮含量及合酶活性的影响

目的：比较脑发育不同阶段低浓度慢性铅暴露对大鼠在体海马一氧化氮含量及合酶活性的差异。方法：分别在仔鼠出生21天、42天、63天时测定对照组、断乳后暴露组、母体暴露组和持续暴露组仔鼠血铅含量和海马NO含量和NOS活性,并与对照组进行比较。结果：各暴露组在不同时间血铅含量均高于对照组（P〈0.05）。断乳后铅暴露组和持续铅暴露组NOS活性与对照组相比均有显著性差异（P〈0.05）,出生21天时明显高于对照组,而42天和63天明显低于对照组。持续暴露组NO含量与对照组相比有明显差异,出生21天时明显高于对照组,而42天和63天明显低于对照组。结论：脑发育任一阶段的慢性铅暴露均对海马NO含量和NOS活性有影响。与发育成熟海马相比,未成熟期海马对铅的神经毒性更为敏感,突触可塑性更易受损。     

不同阶段铅暴露对大鼠妊娠结局及胎盘MMP-9表达的影响

目的通过观察孕期不同时段铅暴露对妊娠结局及胎盘MMP-9的表达影响,评价孕早期、孕后期及孕全程铅暴露的毒性特点及毒性机制。方法采用原子吸收光谱仪测定孕期不同阶段低水平铅暴露后的大鼠孕末期血铅水平。0.025%醋酸铅对实验组孕鼠染毒,根据大鼠孕期3周推算足月剖宫产,观察统计异常分娩情况,记录胎盘质量、仔鼠数、仔鼠质量。免疫组化法测定胎盘滋养细胞MMP-9的表达。结果孕早期染铅对孕末期血铅水平及胎盘质量的影响较大,孕晚期染铅对仔鼠重量的影响较明显,孕全程染铅对孕末期血铅水平、胎盘质量及仔鼠质量均有明显影响,孕全程染铅组其胎盘MMP-9表达下降。结论铅具有生殖毒性及胚盘毒性,孕期不同时段铅暴露导致不同的妊娠结局。胎盘MMP-9表达下降可能是铅致胎盘损伤的病理机制之一。     

Intake and hedonics of calcium and sodium during pregnancy and lactation in the rat

These experiments sought to distinguish whether increased calcium intake during pregnancy and lactation in the rat is due to arousal of a specific calcium appetite, with altered taste hedonics, as occurs with sodium depletion, to reduced taste sensitivity, or to the hyperdipsia of reproduction. We find that, during pregnancy and lactation, CaCl(2) intake is not increased more (in fact less) than intakes of control tastants, MgCl(2) and quinine HCl, and multiparous dams do not have a greater calcium intake than primaparous dams. Changes in taste reactivity to CaCl(2) and to NaCl do not correlate with changes in intake of these minerals during pregnancy or lactation, suggesting that alterations in hedonics or sensitivity do not explain the increased intake of these minerals. Taken together with the increased intake of all the tastants, it may be that the increased intakes of calcium and sodium during reproduction are not due to respective specific appetites or to a general mineral appetite but rather to the reproduction-increased ingestion that may meet all the dam's increased mineral and nutrient requirements. Differences in the degree of increased intakes of tastes may be due to specific alterations in their transduction during reproduction.     

Morphometric effects of exposure to lead during the preweaning period on the hippocampal formation of aging rats

Our previous morphologic studies in the rat demonstrated that exposure to lead during the preweaning period induced delays in the maturation of late-developing regions of the hippocampal formation at 15 days of age, followed by normal development or hypertrophy of the same areas in young adulthood. The present study was carried out to determine whether or not subtle or latent effects of such exposure to lead may be unmasked with the additional challenge of aging. To do this, mid-dorsal sections of the hippocampal formation from middle-aged (578–631 days old) Long-Evans control rats and from rats exposed to lead from birth until weaning via dams drinking 0.2% lead acetate were analyzed by light and electron microscopy. Exposure to lead did not alter areas of either neuropil or neuronal layers of the hippocampus or the dentate gyrus or the numbers per section or numerical densities (numbers per unit area) of neurons in hippocampal CA3 stratum pyramidale or dentate stratum granulosum. It did reduce mean size of complex invaginated mossy fiber synapses without altering their numbers in the proximal (close to dentate gyrus) mossy fiber zone, which was the zone also affected at 15 and 90 days of age in our previous studies.     

Morphometric effects of exposure to lead during the preweaning period on the hippocampal formation of aging rats

Our previous morphologic studies in the rat demonstrated that exposure to lead during the preweaning period induced delays in the maturation of late-developing regions of the hippocampal formation at 15 days of age, followed by normal development or hypertrophy of the same areas in young adulthood. The present study was carried out to determine whether or not subtle or latent effects of such exposure to lead may be unmasked with the additional challenge of aging. To do this, mid-dorsal sections of the hippocampal formation from middle-aged (578–631 days old) Long-Evans control rats and from rats exposed to lead from birth until weaning via dams drinking 0.2% lead acetate were analyzed by light and electron microscopy. Exposure to lead did not alter areas of either neuropil or neuronal layers of the hippocampus or the dentate gyrus or the numbers per section or numerical densities (numbers per unit area) of neurons in hippocampal CA3 stratum pyramidale or dentate stratum granulosum. It did reduce mean size of complex invaginated mossy fiber synapses without altering their numbers in the proximal (close to dentate gyrus) mossy fiber zone, which was the zone also affected at 15 and 90 days of age in our previous studies.     

The protective role of ascorbic acid on hippocampal CA1 pyramidal neurons in a rat model of maternal lead exposure

Oxidative stress is a major pathogenic mechanism of lead neurotoxicity. The antioxidant ascorbic acid protects hippocampal pyramidal neurons against cell death during congenital lead exposure; however, critical functions like synaptic transmission, integration, and plasticity depend on preservation of dendritic and somal morphology. This study was designed to examine if ascorbic acid also protects neuronal morphology during developmental lead exposure. Timed pregnant rats were divided into four treatment groups: (1) control, (2) 100 mg/kg ascorbic acid once a day via gavage, (3) 0.05% lead acetate in drinking water, and (4) 0.05% lead + 100 mg/kg oral ascorbic acid. Brains of eight male pups (P25) per treatment group were processed for Golgi staining. Changes in hippocampal CA1 pyramidal neurons’ somal size were estimated by cross-sectional area and changes in dendritic arborization by Sholl’s analysis. One-way ANOVA was used to compare results among treatment groups. Lead-exposed pups exhibited a significant decrease in somal size compared to controls (P < 0.01) that was reversed by cotreatment with ascorbic acid. Sholl’s analysis revealed a significant increase in apical dendritic branch points near cell body (P < 0.05) and a decreased total dendritic length in both apical and basal dendritic trees of CA1 neurons (P < 0.05). Ascorbic acid significantly but only partially reversed the somal and dendritic damage caused by developmental lead exposure. Oxidative stress thus contributes to lead neurotoxicity but other pathogenic mechanisms are also involved.     

Heart period variability during estrogen exposure and withdrawal in female rats

Heart period, heart period variability, and an estimate of vagal tone were evaluated during estrogen exposure and withdrawal in ovariectomized, freely moving female rats. Spectral analysis was used to quantify the respiratory component of heart period variability (V?), which has been found to be sensitive to alterations of vagal tone to the heart. During estrogen withdrawal, V? decreased significantly and was accompanied by a decrease in heart period. There were no significant differences in heart period or V? between the experimental (estrogen) group and the control (no estrogen) group during estrogen exposure. Total heart period variability did not differ significantly from controls during estrogen withdrawal but it did exhibit an increase during estrogen exposure. In this experiment V? appeared to be more sensitive to changes in estrogen levels than total heart period variability. These data suggest that decreases in cardiac vagal tone and heart rate occur during estrogen withdrawal.     

低水平铅暴露人胎盘组织诱导型和内皮型一氧化氮合酶的表达及意义

目的探讨孕期低水平铅暴露对胎盘组织诱导型和内皮型一氧化氮合酶的表达及其与铅水平的关系。方法2005年2月至2006年12月孕期外周血铅水平大于30μg/l的67例孕妇,根据铅水平分组,血铅水平30μg/l-60μg/l的孕妇35例为A组;血铅水平在60μg/l-100μg/l的孕妇32例为B组。检测胎盘中一氧化氮合酶系统表达。结果低水平铅暴露下诱导型和内皮型一氧化氮合酶在各组胎盘中的表达均分布在合体滋养细胞、细胞滋养细胞、微小血管内皮细胞、蜕膜细胞、绒毛间纤维细胞(villus fibrocyte)的胞浆,定位显示无显著差异;高血铅组的表达水平与强度显著高于低铅水平组(P<0.05)。结论金属铅可诱导发育中胎盘组织诱导型和内皮型一氧化氮合酶产生,胎盘NOS酶活性上升,能够改善子宫-胎盘血循环障碍,抵御铅毒性,维持正常妊娠的进行。     

钙及活性氧在大鼠肾缺血再灌流损伤中的作用

目的和方法 :应用电镜细胞化学方法 ,对缺血 -再灌流损伤过程中活性氧的产生及细胞内钙变化情况进行研究。结果 :缺血期 ,细胞内钙明显增多 ,而此时尚无H2 O2 产生 ;缺血后再灌流早期H2 O2 大量产生 ,细胞内钙与缺血期类似 ;再灌流晚期H2 O2 产生有所减少 ,而细胞内钙持续增高。结论 :钙及活性氧都参与缺血再灌流损伤 ,但其参与时机及作用并不相同。     

钙及活性氧在大鼠肾缺血再灌流损伤中的作用

目的和方法:应用电镜细胞化学方法,对缺血-再灌流损伤过程中活性氧的产生及细胞内钙变化情况进行研究。结果:缺血期,细胞内钙明显增多,而此时尚无H₂O₂产生;缺血后再灌流早期H₂O₂大量产生,细胞内钙与缺血期类似;再灌流晚期H₂O₂产生有所减少,而细胞内钙持续增高。结论:钙及活性氧都参与缺血再灌流损伤,但其参与时机及作用并不相同。     

Effects of sodium on the calcium paradox in rat hearts

Reduction of the Na concentration in the Ca-free perfusion solution reduces the amount of myoglobin released by the cells when Ca is readmitted if sucrose is used to replace NaCl under mild hypothermia. When salts like cholinechloride or LiCl are used instead of sucrose, no protection is seen at any temperature. The temperature threshold above which myoglobin loss sharply increases is lowered by prolonged Ca depletion or by the addition of EGTA to the Ca-free solution. Protection by sucrose does not occur in the presence of EGTA. An increase of cell Na induced by strophanthidin during the Ca depletion phase has no effect on myoglobin release. The exponential decline in twitch tension in the early phase of Ca deprivation has the same half-live (T _1/2) for Ca-free solutions containing 145 mM Na or 35 mM Na (110 mM Li or choline), but itsT _1/2 is prolonged if sucrose is used to replace NaCl. When 5 mM EGTA is added to the Ca-free solutions, theT _1/2 is shortened and is not changed by the replacement of NaCl with sucrose. The rate of washout of Ca within the first 20 s of Ca depletion has a similar time course in a normal Na or in a Li and low Na solution. In a sucrose and low Na solution the rate of the Ca efflux is reduced. The addition of EGTA increases this rate and abolishes the slowing effect of a sucrose and low Na solution. Therefore myoglobin release during the Ca paradox does not depend on the Na gradient across the sarcolemma. Na⁺, like other cations, probably enhances the displacement of Ca²⁺ from critical binding sites during Ca-free perfusion, which predisposes the cells to the paradox.