胚胎期铅暴露对子代大鼠运动协调能力的影响及可能机制

Effects of embryonic lead exposure on motor function and balance ability in offspring rats and possible mechanisms

目的探讨胚胎期铅暴露对子代大鼠运动协调能力的影响及可能机制。方法采用Sprague-Dawley大鼠孕期自由饮用0.1%(低剂量铅暴露组)和0.2%(高剂量铅暴露组)醋酸铅溶液的方法建立胚胎期铅暴露模型,并设空白对照组。将各组母鼠娩出的雄性仔鼠纳入研究,其中空白对照组12只,低剂量铅暴露组10只,高剂量铅暴露组9只。应用转体实验和衣架实验观察仔鼠运动、协调能力;各组随机取8只大鼠,应用免疫组化、改良Timm's染色法分别观察各组大鼠海马c-Fos蛋白表达及苔藓纤维发芽(MFS)情况。结果高剂量铅暴露组转体时间长于正常对照组和低剂量铅暴露组(P<0.05),低剂量铅暴露组转体时间亦长于正常对照组(P<0.05)。高剂量铅暴露组平衡运动得分低于正常对照组和低剂量铅暴露组(P<0.05),低剂量铅暴露组平衡运动得分亦低于正常对照组(P<0.05)。高剂量铅暴露组海马CA1区c-Fos阳性细胞面积百分比高于正常对照组和低剂量铅暴露组(P<0.05),低剂量铅暴露组c-Fos阳性细胞面积百分比亦高于正常对照组(P<0.05)。高剂量铅暴露组CA3区及齿状回MFS的半定量评分均高于正常对照组和低剂量铅暴露组(P<0.05);低剂量铅暴露组CA3区及齿状回MFS的半定量评分亦高于正常对照组(P<0.05)。结论胚胎期铅暴露损害子代大鼠运动协调能力,该变化可能与海马CA1区c-Fos蛋白表达增加及海马CA3区、齿状回发生异常MFS有关。

Objective To explore the effects of embryonic lead exposure on motor function and balance ability in offspring rats and the possible mechanisms. Methods An animal model of embryonic lead exposure was prepared with the use of pregnant Sprague-Dawley rats freely drinking 0.1%（low-dose group, LG） or 0.2%（high-dose group, HG） lead acetate solution. A normal control group（NG） was also set. The male offspring rats of these pregnant rats were included in the study, consisting of 12 rats in the NG group, 10 rats in the LG group, and 9 rats in the HG group. The offspring rats＇ motor function and balance ability were evaluated using body turning test and coat hanger test. Eight rats were randomly selected from each group, and immunohistochemistry and Timm′s staining were employed to measure the expression of c-Fos and mossy fiber sprouting（MFS） in the hippocampus. Results The HG group had a significantly longer body turning time than the NG and LG groups（P〈0.05）, and the LG group had a significantly longer body turning time than the NG group（P〈0.05）. The HG group had a significantly lower score of balance ability than the NG and LG groups（P〈0.05）, and the LG group had a significantly lower score of balance ability than the NG group（P〈0.05）. The area percentage of c-Fos-positive neurons in the hippocampal CA1 region was significantly higher in the HG group than in the other two groups（P〈0.05）, and it was significantly higher in the LG group than in the NG group（P〈0.05）. The semi-quantitative scores of MFS in the hippocampal CA3 region and dentate gyrus were significantly higher in the HGgroup than in the other two groups（P〈0.05）, and they were significantly higher in the LG group than in the NG group（P〈0.05）. Conclusions Embryonic lead exposure could impair the offspring rats＇ motor function and balance ability. These changes may be related to increased c-Fos expression in the hippocampal CA3 region and abnormal MFS in the hippocampal CA3 region and dentate gyrus.