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出生前本地区大气细颗粒物暴露对大鼠心血管系统的影响及其机制研究1.1 目的采用福州地区收集的PM2.5配制悬液进行气道内滴注,通过配子发育期和胎鼠宫内发育期暴露制作PM2.5暴露动物模型,从多层面探讨不同剂量PM2.5暴露对心血管系统的影响及可能机制。
1.2方法SD大鼠随机分为4组,每组8只:对照组、低剂量染毒组(0.26μg/μl的PM2.5混悬液,相当于大气PM2.5浓度35μg/m3)、中剂量染毒组(0.55μg/μl的PM2.5混悬液,相当于大气PM2.5浓度75μg/m3)、高剂量染毒组(1.10μg/μl的PM2.5混悬液,相当于大气PM2.5浓度150μg/m3)。
采用本地区收集的PM2.5配制悬液进行气道内滴注,三天剂量一次性给予,每次30μl,对照组予等量磷酸盐缓冲液(PBS),暴露时间由孕前3周至产后。
孕鼠产仔后,记录仔鼠数量并记录活产数、死产数及外观异常的仔鼠。
母鼠与仔鼠共同饲养至产后21d取材。
高剂量组母鼠随机选取两只行肺部组织病理学检查。
仔鼠心脏行病理组织学检查及TUNEL法检测心肌细胞凋亡、电镜观察心脏组织超微结构变化。
Western blotting法检测仔鼠心脏组织GATA4、Nkx2-5、caspase3蛋白表达及RT-q PCR法检测m RNA的表达。
ELISA法检测仔鼠血浆中TNF-α、IL-1β的水平。
1.3 结果1.3.1 比较各实验组与对照组的每窝仔鼠数及雄性仔鼠或雌性仔鼠出生0天、7天、14天及21天体重情况,均无统计学差异。
1.3.2 光镜下,高剂量组的母鼠肺部可见颗粒物的沉积及肺部炎性病变。
高剂量染毒组仔鼠心脏中可见心肌细胞排列较紊乱、胞浆较稀疏等改变。
1.3.3 电镜下,中高剂量组仔鼠心脏出现核染色质、线粒体、肌纤维等心肌结构改变且以高剂量组为甚。
1.3.4 中、高剂量PM2.5暴露能下调仔鼠心脏Nkx2-5蛋白的表达,高剂量暴露组中Gata4蛋白的表达也较对照组明显下调(P 均<0.05)。
•492•毒理学杂志2020年12月第34卷第6期J Toxicol December2020Vol.34No.6中图分类号:R114文献标识码：A 文章编号:1002-3127(2020)06-0492-05・实验研究・不同粒径微塑料颗粒亚急性染毒对雄性小鼠生殖毒性的影响田坤明，陈秋(遵义医科大学公共卫生学院环境卫生系，贵州遵义563006)【摘要】目的微塑料可在低等生物和水生生物中导致生殖毒性和胚胎发育障碍，本研究将进一步探讨其是否影响哺乳动物生殖功能。
方法雄性C57BL/6小鼠分为4组，分别为对照(生理盐水)组,0.I J和10“m组，每组10只小鼠。
经灌胃染毒剂量为5mg/kg-bw不同粒径微塑料颗粒28<1。
染毒完毕后用透射电子显微镜观察睾丸超微结构损伤；苏木素-伊红(HE)染色分析睾丸组织病理改变；谷胱甘肽(GSH)、超氧化物歧化酶(SOD)和丙二醛(MDA)试剂盒检测睾丸组织氧化应激反应；精子HE染色观察精子质量。
结果3个粒径微塑料均能造成睾丸生精细胞凋亡、自噬和内质网水肿，但是，精子质量未发生明显改变。
此外，睾丸组织同样未发生明显病理改变，GSH.SOD和MDA检测同样发现睾丸组织未发生氧化应激反应。
结论亚急性染毒微塑料可能会给雄性生殖功能造成潜在毒性，应进一步研究长期染毒纳米和微米尺度微塑料对雄性生殖功能的影响。
【关键词】微塑料；生殖毒性；氧化应激The effect of sub-acute exposure of microplastics on the male micereproductive functionTIAN Kun-ming,CHEN Qiu(Department of environment health,School of public health,Zunyi Medical University,Zunyi Guizhou563006,China) [Abstract]Objective Previous studies indicated that MPs possess reproductive and developmental toxicity in lower organisms and aquatic organisms,to investigate whether MPs could generate reproductive toxicity in mammal animal.Methods Male C57BL/6mice were divided into four groups:control group(saline),0.1,1|im,and10|im group,and10mice per group,respectively.The mice were intragastric administration with5mg/kg•bw indicated microplastics for28days.The transmission electron microscopy was employed to observed the ultrastructural changes of testis；The pathological changes of testis were detected by HE staining.GSH,SOD,and MDA kidts were used to test the oxidative reaction of testis and HE staining of sperm to determine the quality of sperm.Results Three diameter-scale microplastics could result in the ultrastructural changes of spermatogonia,including apoptosis,autophagy,and endoplasmic reticulum edema after28days administration.However,it was not found that significant pathological changes in testis tissue.Additionally,the oxidative stress and sperm quality were also not influenced by the three diameter-scale microplastics.Conclusion Microplastics could lead to ultrastructural changes of testis,but not pathological alterations and reproductive toxicity.[Key words]Microplastics；Reproductive toxicity；Oxidative stress微塑料是指直径小于5的塑料碎屑，由Thompson等1「首次在《Science》杂志中提出。
母鼠有机磷农药暴露对着床前期小鼠胚胎的细胞遗传学及生长发育的影响(英文)田英;石川仁;山内彻【期刊名称】《环境与职业医学》【年(卷),期】2004(21)5【摘要】[目的 ]研究妊娠初期有机磷农药暴露对母体生殖功能 ,对子代细胞遗传学及生长发育的影响。
[方法 ]以有机磷农药敌百虫为受试物 ,以着床期胚胎为研究对象 ,以反映染色体异常的微核形成和反映胚胎生长发育状况的构成细胞数为指标。
孕鼠腹腔注射 10 0或 2 0 0mg/kg剂量的敌百虫溶液 ,3d后 ,在体视显微镜下从其子宫中取出胚胎 ,进行其形态学分析 ,微核试验及胚胎构成细胞数的分析。
[结果 ]敌百虫暴露组的胚胎微核发生率明显高于对照组 ,分别为 2 0 0mg/kg暴露组为16 9% ,10 0mg/kg暴露组 16.1% ,对照组为 5 .3 % ,并有明显的剂量反应关系。
此外 ,母鼠暴露于敌百虫 ,可造成子代生长发育迟缓 ,表现为胚胎构成细胞数明显下降 ( 2 0 0mg/kg组 44 .1,对照组 5 4.7)。
[结论 ]妊娠初期有机磷农药暴露对着床前期胚胎的细胞遗传学及生长发育有明显影响。
着床前期小鼠胚胎的微核试验是评价母体早期暴露有机磷农药导致子代细胞遗传学改变的简便、灵敏的指标 ,本结果为进一步对着床后胚胎的研究。
【总页数】3页(P391-393)【关键词】暴露;胚胎;着床前;细胞遗传学;有机磷农药;对照组;细胞数;生长发育;敌百虫;母鼠【作者】田英;石川仁;山内彻【作者单位】上海第二医科大学公共卫生学院预防医学教研室;日本三重大学医学部公共卫生教研室【正文语种】中文【中图分类】R321.33;R733【相关文献】1.妊娠中末期邻苯二甲酸(2-乙基己基)酯暴露对母鼠妊娠结局及子鼠生长发育的影响 [J], 丁瑜;高宇;施蓉;周义军;田英2.着床前大、小鼠胚胎暴露于敌枯双的发育毒性研究 [J], 张天宝;刘建;等3.补肾安胎方对胚泡着床障碍小鼠胚胎着床局部COX-2蛋白和mRNA表达的影响 [J], 张明敏;董莉萍;程亮亮4.母鼠低剂量敌百虫染毒对着床前期胚胎细胞发育及微核的影响 [J], 周淑芳;沈莉;高宇;施蓉;周义军;丁瑜;王沛;田英5.极低频率电磁场对小鼠生育能力及着床前期子宫内膜和输卵管上皮细胞高度的影响(英文) [J], Farzad RAJAEI;Nasim BORHANI;Fatemeh SABBAGH-ZIARANI;Farhad MASHAYEKHI因版权原因，仅展示原文概要，查看原文内容请购买。
妊娠期PM2.5,暴露影响子代鼠主要脏器发育郑昕蕊;赵会;田换兵;张红霞;张雪莉;吴洪娟;于丽【摘要】目的探讨妊娠期大气细颗粒物PM2.5(颗粒直径≤ 2.5μm)暴露对子代鼠主要脏器发育的影响.方法孕鼠随机分为空白组、对照组、PM2.5低剂量组、PM2.5中剂量组、PM2.5高剂量组.利用气管滴注方法,建立小鼠妊娠期PM2.5暴露模型.通过HE染色和PAS反应,观察妊娠期暴露于PM2.5后新生子代鼠主要脏器的病理形态学改变,通过电子显微镜观察细胞超微结构变化.结果与空白组和对照组相比,PM2.5模型组新生子代鼠心、肝、脾、肺和肾组织结构均受损,可见炎症等病理改变.子代鼠主要脏器超微结构出现不同程度的细胞核周隙局部增宽、自噬体增多、线粒体嵴模糊和断裂等变化.结论妊娠期暴露于PM2.5可导致新生子代鼠心、肝、脾、肺、肾等主要脏器出现组织形态异常.这可能是PM2.5致生后远期慢性疾病发生的解剖学基础和发育源性病因.%Objective To investigate the effects of atmospheric particulate matter (AD≤2.5μm,PM2.5) exposure on the development of major organs in offspring mice during pregnancy.Method Pregnant mice were randomly divided into blank,control,PM2.5low,medium and high dose groups.Rapid mice trachea drip improved method was used to establish the pregnant mice PM2.5 exposured model.The pathological changes of main organs in neonatal mice exposed to PM2.5 during pregnancy were evaluated by HE staining and PAS reaction,while the cellular ultrastructural changes were analyzed by transmission electron microscopy.Results Compared to the blank and control groups,the tissue organization of major organs includingheart,liver,spleen,lung and kidney in neonatal mice of PM2.5 group wereabnormal with obvious inflammatory infiltration.Changes at ultrastructural level were also observed in PM2.5 group,including widened perinuclear gap,increased autophagosomes,and mitochondrial cristae fragmentation.Conclusion PM2.5 exposure during pregnancy results in abnormal tissue organization and morphology of major organs in neonatal mice,which may potentially be the anatomical and pathological root cause of chronic diseases in later life.【期刊名称】《中国组织化学与细胞化学杂志》【年(卷),期】2017(026)004【总页数】7页(P366-372)【关键词】妊娠期PM2.5暴露;子鼠;主要脏器;炎症【作者】郑昕蕊;赵会;田换兵;张红霞;张雪莉;吴洪娟;于丽【作者单位】潍坊医学院临床医学院,潍坊261053;潍坊医学院临床医学院,潍坊261053;潍坊医学院生物科学与技术学院,潍坊261053;潍坊医学院临床医学院,潍坊261053;潍坊医学院临床医学院,潍坊261053;潍坊医学院临床医学院,潍坊261053;潍坊医学院临床医学院,潍坊261053【正文语种】中文【中图分类】R715.3大气细颗粒物PM2.5（fine particulate matter with diameter of ≤2.5μm）是指空气动力学当量直径小于等于2.5μm的颗粒物，可造成机体多个系统不同程度的损伤[1]。
孕期和哺乳期暴露PM2.5对子代小鼠生长发育的影响及维生素C和槲皮素的干预研究张敏佳;刘伟;周雅琳;李雍;冯金秋;范爱琴;许雅君【摘要】目的研究孕期和哺乳期暴露PM2.5对子代小鼠生长发育的影响,探索维生素C及槲皮素是否具有改善孕期和哺乳期暴露PM2.5对子代小鼠生长发育影响的能力. 方法收集2016年非采暖期北京市某地区PM2.5样品,以无菌PBS配制不同浓度的PM2.5溶液.将健康ICR孕鼠随机分为6组:空白对照组、PM2.5低、中、高剂量组,VC干预组和槲皮素干预组.各组母代小鼠于孕期及哺乳期共进行8次气管滴注,PM2.5低、中、高剂量组分别给予3.75、7.5、15 mg/kg PM2.5溶液,VC 和槲皮素干预组给予15 mg/kg PM2.5溶液,空白对照组给予干净滤膜洗脱液;各组母代小鼠于孕期和哺乳期每天灌胃,VC及槲皮素干预组分别予以100 mg/kg的VC或槲皮素溶液,其他各组予以溶剂.观察记录母鼠和仔鼠整个实验周期内体重、进食量,和子代小鼠生长发育、神经发育指标达标的时间. 结果子代小鼠PM2.5高剂量组PND14的体重均明显低于空白对照组(P＜0.05);予代雄性小鼠PM2.5剂量组门齿萌出(下)、睾丸下降、平面翻正、负向地性、悬崖回避达标时间明显比空白对照组迟缓(P＜0.05),VC、槲皮素干预组平面翻正、悬崖回避达标时间比PM2.5高剂量组明显改善(P＜0.05),槲皮素干预组门齿萌出(下)达标时间明显改善(P＜0.05);子代雌性小鼠PM2.5剂量组门齿萌出(上、下)、负向地性、悬崖回避、空中翻正达标时间明显比空白对照组迟缓(P＜0.05),VC、槲皮素干预组悬崖回避、空中翻正达标时间比PM2.5高剂量组明显改善(P＜0.05). 结论孕期和哺乳期一定剂量PM2.5暴露影响子代小鼠早期生理及神经反射的发育,VC和槲皮素干预可在一定程度上改善此不良影响.%Objective [ABSTRACT] Objective:To study the effects of PM2.5 exposure on the growth and development of offspringmice during pregnancy and lactation,and to investigate whether VC and quercetin can improve the growth and development of mice exposed to PM2.5 during pregnancy and lactation.Methods PM2.5 samples were collected from an area in Beijing during the non-heating period in 2016,and different concentrations of PM2.5 solutions were prepared by sterile PBS.Healthy ICR pregnant mice were divided into 6 groups randomly:the control group,the PM2.5 low,medium and high dose group,the VC intervention group,and the quercetin interventiongroup.Mother mice in each group were given solutions for 8 times by intratracheal instillation during pregnancy and lactation;PM2.5low,medium and high dose groups were given 3.75,7.5,15 mg/kg PM2.5 solution respectively,VC and quercetin intervention group were given 15 mg/kg PM2.5 solution,and the control group was given a clean filter elution liquid.Mother mice were administrated by intragastric administration everyday;VC and quercetin intervention group were treated with 100 mg/kg VC or quercetin respectively,and the other groups were treated with solvent.The changes of body weight,food intake of all animals,and growth and neural-developmental indexes of all spring were observed in the whole experimental period.Results The weight of offspring in PND14 in the PM2.5 high dose group was significantly lower than that in the control group (P ＜0.05,P ＜0.01).Offspring in the PM2.5 groups had more developmental problems than animals in the control group (P ＜ 0.05 and P ＜ 0.01) and offspring in the intervention groups had less developmental problems than animals in the PM2.5 high dose group (P ＜0.05 and P ＜ 0.01).Conclusion Certain doses of PM2.5 exposure during pregnancy and lactation affect the development of early physiology and nerve reflex in offspring mice,and the intervention of VC and quercetin can improve the adverse effects to some extent.【期刊名称】《中国生育健康杂志》【年(卷),期】2018(029)001【总页数】7页(P25-30,36)【关键词】PM2.5;生长发育;维生素C;槲皮素【作者】张敏佳;刘伟;周雅琳;李雍;冯金秋;范爱琴;许雅君【作者单位】100191,北京大学公共卫生学院营养与食品卫生学系;100191,北京大学公共卫生学院营养与食品卫生学系;100191,北京大学公共卫生学院营养与食品卫生学系;100191,北京大学公共卫生学院营养与食品卫生学系;100191,北京大学公共卫生学院营养与食品卫生学系;100191,北京大学公共卫生学院营养与食品卫生学系;100191,北京大学公共卫生学院营养与食品卫生学系;食品安全毒理学研究与评价北京市重点实验室【正文语种】中文近年来，中国多次爆发大面积的雾霾事件，我国许多省份雾霾天气频发。
