邻苯二甲酸二异壬酯致小鼠肾组织氧化损伤的研究

邻苯二甲酸二异壬酯是一种新型替代增塑剂,对其毒性研究已受到广泛关注。为探究邻苯二甲酸二异壬酯对肾组织的氧化损伤作用,将昆明小鼠随机分为5组,包括1个阴性对照组、4个邻苯二甲酸二异壬酯染毒组,按0.5、5、50和500 mg·kg-1四个剂量水平灌胃染毒14天。制备小鼠肾组织切片进行病理学观察,以肾组织匀浆测定活性氧(reactive oxygen species,ROS)、还原型谷胱甘肽(glutathione,GSH)、丙二醛(malondialdehyde,MDA)和8-羟基脱氧鸟苷(8-hydroxy-2-deoxyguanosine,8-OHd G)的含量,以肾组织细胞悬液测定DNA-蛋白质交联(DNA-protein Crosslink,DPC)系数。随着邻苯二甲酸二异壬酯染毒剂量的升高,小鼠肾组织的损伤程度加重,ROS、MDA、8-OHd G含量和DPC系数逐渐上升,GSH含量逐渐降低,各指标均呈一定剂量-效应关系。染毒剂量为5 mg·kg-1时,ROS、DPC系数差异有统计学意义(P0.05,P0.01);染毒剂量为50 mg·kg-1和500 mg·kg-1时,ROS、GSH、8-OHd G、MDA含量和DPC系数差异均有统计学意义(P0.05,P0.01)。结果表明较高剂量(≥50 mg·kg-1)邻苯二甲酸二异壬酯可造成小鼠肾组织氧化损伤。     

CdTe/ZnSQDs在小鼠肾脏中的药代动力学特征

为了解Cd Te/Zn SQDs(Cd Te/Zn S量子点)在小鼠肾脏中的药代动力学特征,选择雄性ICR(Institute of Cancer Research)小鼠为动物模型,每只单次尾静脉注射5 nmol的Cd Te/Zn SQDs(粒径约为6 nm,最大发射波长590 nm)。在尾静脉注射Cd Te/Zn SQDs 15 min、1 h、6 h、24 h、72 h、168 h、2 w、4 w和6 w时剖取小鼠的肾脏,消化后使用电感耦合等离子体质谱(ICP-MS)检测其中的Cd(镉)和Te(碲)含量,Cd和Te在小鼠肾脏中浓度随时间的变化均呈现先增加后降低的趋势,Cd和Te含量分别在168 h和72 h时达到峰值(60.42±8.85)ng·g~(-1)和(18.69±0.97)ng·g~(-1),之后逐渐下降,将二者的含量以摩尔比表示,随着给药时间的延长,摩尔(Cd):摩尔(Te)由2.71:1逐渐变成1.39:1。利用3P87计算Cd和Te在肾脏中的药代动力学参数,结果发现Cd和Te在肾脏中的Vd(表观分布体积)分别为(823.14±82.76)g·kg~(-1)和(686.28±53.13)g·kg~(-1)(P0.05);AUC(药物浓度-时间曲线下面积)分别为(24.48±2.52)μg·g~(-1)·h和(7.41±0.60)μg·g~(-1)·h(P0.01);CL(清除率)分别为(0.90±0.11)g·kg~(-1)·h~(-1)和(1.02±0.13)g·kg~(-1)·h~(-1)(P0.05);t1/2(半衰期)分别为(617.02±8.57)h和(458.21±1.85)h(P0.01)。研究提示Cd和Te在肾脏含量的摩尔比随时间变化不同,QDs在体内发生了化学降解;二者的药代动力学参数不同,Cd在肾脏中的代谢速度明显慢于Te,游离的Cd2+可能引起肾脏毒性。     

DEHP暴露对小鼠神经行为学及脑脂质过氧化物的影响

为研究增塑剂邻苯二甲酸二乙基己酯(Di-2-ethylhexyl phthalate,DEHP)对脑组织造成氧化损伤以及对小鼠神经行为(主要包括学习、记忆能力与情绪)的影响.将24只雄性昆明小鼠随机分成4组,每组6只,分别为对照组(生理盐水),低浓度染毒组(5mg·kg-1DEHP,L组),中浓度染毒组(50mg·kg-1DEHP,M组),高浓度染毒组(500mg·kg-1DEHP,H组).利用Y型电迷宫检验小鼠的学习记忆能力变化,利用悬尾实验和强迫游泳实验检测小鼠抑郁行为的变化.然后取出脑组织,检验活性氧簇(ROS)及丙二醛(MDA)含量.数据显示,染毒组小鼠的学习记忆及行为学控制能力明显低于对照组(p<0.05),并且随DEHP浓度的增大小鼠的学习记忆及行为学控制能力降低.DEHP低、中、高剂量染毒组与对照组氧化应激反应均具有显著性(p<0.05),且呈剂量效应关系.因此,DEHP可导致小鼠学习记忆能力下降、抑郁情绪增加,其分子机制可能涉及DEHP对脑组织造成的氧化损伤.     

口服农药呋喃丹对ICR小鼠致癌性研究

呋喃丹引入我国已有数年,广泛施用于棉田或稻秧田,其污染作用较有机磷农药易防治。关于呋喃丹的“三致”(致突变、致畸变、致癌)试验,已有资料报道它不致畸;高浓度的呋喃丹对鼠伤寒沙门氏菌T_A98菌株有致突变作用。但还没有关于其致癌性的研究报告。本试验对长期口服呋喃丹的ICR小鼠作致癌性研究,旨在为其合理安全地推广使用提供一定的科学依据。     

硝基苯的蓄积毒性和氧化损伤

以小鼠为对象,对硝基苯(NB)的蓄积毒性和氧化损伤进行研究,检测SOD,GSH-Px,CAT,MDA和蛋白质羰基含量.结果表明,蓄积系数(K)为4.76;亚急性试验随着染毒剂量的加大,肾脏和脾脏的MDA含量逐渐升高,CAT,SOD和GSH-Px[酶活性逐渐降低,蛋白质羰基含量呈上升趋势,并表现出明显的剂量效应.表明NB对肾脏和脾脏具有明显的毒性作用,NB可使自由基在机体内累积,引起蛋白质氧化损伤,导致机体发生氧化应激.     

二氧化硫和铅联合染毒对小鼠遗传物质的损伤

运用单细胞凝胶电泳技术研究了SO₂和醋酸铅亚急性联合染毒对雄性小鼠脑、肺、脾、肾细胞DNA的损伤.结果表明,在42mg/m³ SO₂和0.2%醋酸铅单独及联合作用下,小鼠脑、肺、肾、脾细胞DNA迁移距离均比对照组显著增加,而且铅可以加剧SO₂对脑、肾、脾细胞核DNA的损伤程度;SO₂对肺细胞核DNA的损伤程度要比铅的损伤大,小鼠肺细胞核DNA迁移距离在SO₂和醋酸铅联合作用组与醋酸铅单独作用组间有极显著性差异(P<0.01),而与SO₂单独作用组间没有显著性差异.SO₂和醋酸铅均可引起小鼠组织细胞的DNA损伤,它们对脑、肺、脾、肾的损伤程度不同,在一定条件下存在明显的协同效应,可以增强彼此的毒性作用.这意味着SO₂和铅均有引起哺乳动物细胞基因突变的潜在危险,大气SO₂污染与铅的污染可能加剧某些疾病的发生与发展.     

Inhalation of two putative Gulf War toxins by mice

We employed our inhalation methodology to examine whether biomarkers of inflammation and oxidative stress would be produced in mice following inhalation of aerosols containing carbonaceous particles or the vapor of pesticides prevalent during the first Gulf War. Exposure to two putative Gulf War Illness toxins, fine airborne particles and the pesticide malathion, increased biomarkers of inflammation and oxidative stress in Friend virus B (FVB) female mice. Mice inhaling particles 24 h before had increased lung lavage and plasma Leukotriene B4 (LTB₄) (a biomarker of inflammation) and PGF_2α (a biomarker of oxidative stress) levels, lung lavage protein and lung lavage lactic dehydrogenase (LDH) levels. These changes were a function of particle density and exposure time. Compared to particle inhalation, mice inhaling malathion 24 h before had small increase in plasma LTB₄ and PGF_2α levels but no increase in lung lavage LTB₄, lung lavage protein, lung lavage LDH, and lung lavage alveolar macrophage (AM) levels compared to unexposed control mice. AM from particle-exposed mice contained phagocytosed particles, while AM from malathion-exposed mice showed no abnormalities. Our results indicate that inhaling particles or malathion can alter inflammatory and oxidative biomarkers in mice and raise the possibility that these toxins may have altered inflammation and oxidative stress biomarkers in Gulf War-exposed individuals.     

PM2.5对小鼠和H9C2细胞心肌肥大相关因子mRNA表达的影响

用采自太原市4个不同季节的细颗粒物(PM_(2.5))对小鼠心肌细胞H9C2进行染毒后,采用荧光定量PCR技术检测心肌肥大相关因子ANP和TGF-β的mRNA水平.采用浓度分别为0、1、3、10μg·mL~(-1)的冬季PM_(2.5)处理H9C2细胞后,检测心肌肥大相关因子ANP、β-MHC、MMP2和MMP9的mRNA水平.之后分别选取4周龄、4月龄、10月龄C57BL/6雌性小鼠作为实验模型,采用咽后壁滴注的方法用3 mg·kg~(-1) PM_(2.5)暴露4周.采用苏木素-伊红染色(HE)对小鼠心脏组织病理切片进行观察,并检测ANP和β-MHC的mRNA水平.结果发现,与对照组相比,冬季PM_(2.5)诱导H9C2细胞中ANP和TGF-β的mRNA水平升高最为显著;其中,当冬季PM_(2.5)染毒浓度较高时可诱导ANP、β-MHC、MMP2和MMP9的mRNA水平均显著升高.经PM_(2.5)暴露4周后,幼年和老年小鼠心肌细胞核质比显著降低.老年小鼠心脏组织中ANP和β-MHC的mRNA表达水平显著上升.实验表明,冬季PM_(2.5)诱导心肌肥大标志物表达改变的效应要强于其他季节,且有一定的剂量效应关系,而老年小鼠对PM_(2.5)诱导的心肌肥大效应最为敏感.     

Emigration mechanisms in feral house mice – a laboratory investigation of the influence of social structure,population density,and aggression

Emigration in small mammals may be strongly related to social factors, but direct observations of emigrants are rare. Feral house mice (Mus domesticus) were studied using a population cage system that allowed continuous observation of individually marked animals. Mice that left their natal cage and took up residence in cages that could only be reached by crossing a water barrier were defined as emigrants. Six pairs of house mice with their litters were placed in the system, and data on aggressive interactions, body weight, reproduction, mortality and emigration were collected daily. Both sexes emigrated, but males did so twice as often as females. Population density was not correlated with the frequency of aggression, and had no effect on the weight of emigrating individuals. Male emigrants suffered more aggression before emigration than their non-emigrant brothers of the same age; they were aggressively driven out by other males, predominantly by the father. Female emigration depended on the female’s chances of reproduction. The probability of a female reproducing decreased with increasing birth order. Females born in a late litter, who therefore had only a low chance of reproduction, dispersed earlier than those of early litters. Resident males were reproductively suppressed. Male offspring had two different strategies for attaining top rank. They could develop rapidly and reach sexual maturity early on, but face competition with the father, risking being forced to emigrate. Alternatively, they could develop slowly, stay within their family and wait for a chance to take over the dominant position. It is concluded that emigration in male and female feral house mice is caused by intrasexual competition. Received: 13 July 1995/Accepted after revision: 8 June 1996     

氰戊菊酯生理毒物代谢动力学模型的建立

利用生理毒物代谢动力学(PBTK)对小鼠静脉注射农药氰戊菊酯后,氰戊菊酯在体内分布转化代谢过程进行模拟,为评价农药暴露风险提供依据。小鼠静脉注射氰戊菊酯的PBTK模型构建分为5个房室:肝脏、肺、肾脏、充分灌注室和不充分灌注室,各房室内氰戊菊酯的浓度变化率由质量守恒微分方程表示。根据欧拉数值计算方法,对小鼠静脉注射氰戊菊酯后的毒物代谢动力学数据进行模拟。结果模拟预测了小鼠静脉注射0.5 mg·kg-1、2.5 mg·kg-1、10 mg·kg-1氰戊菊酯后血液、肝脏和肺中氰戊菊酯浓度变化曲线。为验证该模型的准确性,对小鼠静脉注射0.77 mg·kg-1氰戊菊酯后血液、肝脏和肺中氰戊菊酯的浓度值变化模拟值与前人的实验测量值进行比较,结果显示模拟值与实验值之间不存在显著性差异。因此利用该方法可以估测小鼠静脉注射氰戊菊酯的毒物代谢动力学数据,为评估农药暴露体内剂量数据提供了便利途径。