大鼠母体镉暴露对胎鼠生长发育及其体内镉分布的影响

发布时间：2018-01-21 13:58

  本文关键词： 镉稳定同位素 胎盘 胎鼠 骨骼 脐血　出处：《山西医科大学》2012年硕士论文　论文类型：学位论文

【摘要】：目的探讨镉是否通过胎盘屏障到达胎鼠体内影响胎鼠生长发育,为进一步研究镉发育毒性的机制提供资料。 方法雌性SPF级SD大鼠40只随机分为2组,即对照组和染镉组,每组20只,对照组大鼠皮下注射去离子水,染镉组大鼠皮下注射40μg/kg体重112Cd2+溶液,每天一次,连续染毒45～58天。第24天开始将所有雌性大鼠与健康雄性大鼠同笼交配,次日晨查到阴栓或精子,定为怀孕第0天。怀孕第20天时对试验大鼠乙醚麻醉后进行解剖,取母鼠和胎鼠主要脏器,具体检测项目和方法如下： (1)镉在母鼠体内的分布：母鼠尿、母鼠血用原子吸收光谱仪(AAS)测定镉含量；用电感耦合等离子体质谱仪(ICP-MS)测母鼠脑、心脏、肝脏、肾脏和胎盘中镉含量。检测母鼠血生化指标、雌二醇(E2)以及尿中视黄醇结合蛋白(URBP).微量白蛋白(MAU)和尿肌酐(CREA)等指标。统计吸收胎率、死胎率、活胎率。 (2)镉对子代影响的研究：胎鼠生长发育指标的分析。用AAS测脐带血镉含量,研究镉是否能够通过胎盘屏障；用ICP-MS测胎鼠脑、心脏、肝脏、肾脏的镉含量,研究镉在胎鼠各脏器中的分布。镉对胎鼠骨骼形成的影响：胎鼠去掉两侧颈部皮肤和脂肪,经过固定、透明、染色、透明脱色后在解剖显微镜下观察胎鼠骨骼形态,研究低剂量镉是否能够引起胎鼠骨骼畸形。 (3)镉对母鼠和胎鼠脏器的病理学影响：取SD大鼠母鼠和胎鼠的脑、心脏、肝脏、肾脏,以及胎盘对其进行固定、脱水、包埋、切片和染色后,在普通光学显微镜下检查以上脏器的细胞形态学改变,研究低剂量镉是否引起母鼠和胎鼠脏器的病理学改变。 结果(1)镉在母鼠体内的分布：①母鼠体内镉分布以及镉负荷：染镉组大鼠脑、心脏、肝脏、肾脏、胎盘的镉含量与对照组相比差异均有统计学意义(P0.01)。染毒第24天和孕期第20天的染镉组母鼠血镉含量均高于对照组血镉,差异均有统计学意义(P0.01)。染镉组大鼠尿镉含量仅在染毒至孕期20天时高于对照组尿镉含量,差异有统计学意义(P0.05)。②母鼠肝、肾功能指标：在染毒第24天和妊娠第20天时,母鼠尿视黄醇结合蛋白含量与对照组之间的差异有统计学意义(P0.01)。染毒第24天和孕第20天时染镉组MAU与对照组MAU之间的差异尚无统计学差异(P0.05)。孕第20天时实验组大鼠血中仅AST和CREA与对照组血中AST和CREA之间差异有统计学意义(P0.01)。③染镉组吸收胎率增高,活胎率降低,母鼠孕20天的雌二醇水平下降,差异均有统计学意义(P0.01)。 (2)镉对子代的影响研究：①染镉组胎盘重量、胎鼠重与对照组相比显著降低,差异有统计学意义(P0.01)。②染镉组胎鼠脐血血镉含量是对照组脐血血镉含量的11倍之多,差异有统计学意义(P0.01)。③染镉组胎鼠脑、心、肝、肾镉含量均较对照组相应脏器镉含量增加,且与对照组之间的差异均有统计学意义(P0.01)。④染镉组胎鼠异常率显著高于对照组,主要表现有鼠掌骨未骨化、胸骨骨化不全和胸骨未骨化。 (3)母鼠和胎鼠脏器的病理学改变：母鼠肝脏、肾脏的病理改变率显著高于对照组(P0.01),主要表现为肾脏轻度弥漫性肾小管上皮细胞空泡化和肝细胞水肿肝细胞肿胀等病变。染镉组和对照组胎盘和胎鼠脏器均未见明显病理改变。 结论应用稳定同位素镉112Cd按40μg112Cd2+/kg体重剂量对雌性SD大鼠进行皮下注射染毒,染毒周期覆盖雌性大鼠四个动情周期(24天)和孕期20天。连续镉染毒可以引起染镉组吸收胎率增高、活胎率下降、胎盘重量和胎鼠重降低,降低孕鼠雌二醇水平。低剂量镉可以通过大鼠胎盘屏障并分布到胎鼠体内的脑、心脏、肝脏和肾脏等多个脏器。并且本实验条件下镉可以引起胎鼠骨骼畸形,阻碍骨骼的形成,主要有胎鼠掌骨未骨化、胸骨骨化不全和胸骨未骨化等。在母鼠体内脏器的分布由高到低依次是肝脏、肾脏、脑、胎盘、心脏。并引起孕鼠肝脏、肾脏功能的损伤和肝肾的病理改变。本试验模拟大鼠一代繁殖实验,建立低剂量染毒模型,与人体的实际接触比较吻合。
[Abstract]:Objective To study the effect of cadmium on the growth and development of fetal mice through placental barrier , and to provide information for further study on the mechanism of cadmium development toxicity . Methods Forty - four female SPF SD rats were randomly divided into 2 groups : control group and Cd - stained group . 20 rats in each group were injected subcutaneously with deionized water and 40 渭g / kg body weight of 112 Cd 2 + solution . The female rats and healthy male rats were injected subcutaneously once a day for 45 - 58 days . ( 1 ) Distribution of cadmium in female mice : determination of cadmium content by atomic absorption spectrometry ( AAS ) in mother rat urine and maternal rat blood ; determination of cadmium content in brain , heart , liver , kidney and placenta by inductively coupled plasma mass spectrometer ( ICP - MS ) . Blood biochemical indexes , estradiol ( E2 ) , and retinol binding protein ( URBP ) in urine were measured . ( 2 ) The effect of cadmium on children ' s growth and development was studied . The content of cadmium in cord blood was measured by AAS . The cadmium contents of fetal rat brain , heart , liver and kidney were measured by ICP - MS . The effects of Cd on the skeletal formation of fetal mice were studied . ( 3 ) The pathological effects of cadmium on the organs of mother and fetal rats were studied : the brain , heart , liver , kidney and placenta of SD rats were fixed , dehydrated , embedded , sectioned and stained . The morphological changes of the above organs were examined under common optical microscope . Results ( 1 ) The distribution of cadmium in mother rat was significantly higher than that of control group ( P0.01 ) . There was no significant difference between the contents of cadmium in the brain , heart , liver , kidney and placenta of the rats in the control group ( P0.01 ) . ( 2 ) The effect of cadmium on filial generation was as follows : ( 1 ) The placental weight of cadmium - stained group and the weight of fetal mice were significantly lower than those in control group ( P0.01 ) . 鈶，

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