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孕期不同阶段铅暴露对大鼠胎盘血栓调节蛋白、核因子-κB表达影响的实验研究
【作者】 邹翠丽；
【作者基本信息】 青岛大学 ， 遗传学， 2010， 硕士
【摘要】 目的：探讨孕期不同阶段铅暴露对大鼠胎盘血栓调节蛋白(thrombomodulin, TM)、核转录因子NF-κB (nuclear ranscription factor-κB, NF-κB)的影响,推测铅暴露对胎盘的损伤机制。方法：108只大鼠随机分为A,B,C,D4组,0.025%醋酸铅对实验组大鼠染毒。根据大鼠孕期3周推算,足月剖宫产,孕末期腹腔静脉取血,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血铅水平。统计记录各组的平均血铅水平。免疫组织化学方法测定大鼠胎盘内TM、NF-κB的表达。应用实时荧光定量PCR检测大鼠胎盘TMmRNA的表达。结果：①实验组大鼠孕末期血铅水平均高于对照组(P<0.01)。受孕大鼠血铅水平与胎盘重量呈负相关(r=—0.652、p<0.01)。②NF-κB的OD值实验组(B、C、D组)明显高于对照组(A组),且差别具有统计学意义(P<0.01)。除了B、C两组比较以外,任意两组在NF-κB表达的差异都具有显著性意义。③胎盘组织中TM蛋白表达与TM mRNA的表达趋势基本一致,实验B、C、D组呈依次升高,与A组(对照组)比较差异有显著性(P<0.01),其中B组和C组低于A组低,而D组明显高于A组。结论：①孕期不同阶段的铅暴露对NF-κB的表达产生不同的影响,其对胞浆细胞器的损害可能干扰母体与胎儿之间营养物质和氧气的交换,这可能是导致异常妊娠的原因之一。②孕期不同阶段铅暴露可影响TM基因mRNA和蛋白的表达；TM表达异常引起的消耗性血管内凝血和胎盘血管化生可能是孕期铅暴露致胎盘损伤的重要机制之一。
【Abstract】 Objective To investigate the toxicity of lead exposure on the placenta at different dosages and the relationship with placental expression of NF-κB and thrombomodulin.Methods 108 wistar rats were randomly divided into four groups (A,B,C,D)for consumption of water with or without 0.025% lead acetate during various gestational periods; Blood lead content was determined by atomic absorption spectrophotometry. Placental NF-κB and thrombomodulin expression was evaluated by immunohistochemistry. TM mRNA was evaluated by fluorescent quantitative real time PCR.Results Maternal blood lead levels in the rats was significantly higher compared to controls (P<0.01). Maternal blood lead levels in the rats negatively correlated with placental weight(r=0.652, p<0.01). On the other hand, placental expression of NF-κB in lead-exposed rats was significantly higher than that in controls(P<0.01). The placental expression of TM mRNA in lead-exposed rats was corresponding with the expression of TM protein. The tendency was increased continuous in group B, group C and group D. The TM expression in group B and group C was lower than in group A, whereas the expression in group D was higher than in group A (P<0.01).Conclusion Lead exposure at various gestational periods produce varied effects, with NF-κB activation following lead exposure.Injury to cytoplasmic organelles may interfere with the nutrition and oxygen exchange between mother and fetus, which may be contribute to abnormal pregnancy outcomes. On the other hand, Lead exposure on rat placental may affect the expression of thrombomodulin. This effect could be associated with impairment in the placenta and may represent one mechanism by which prenatal lead exposure, caseuse impairment by consumptive intravascular coagulation and placental vascularization.