铅对大鼠脑区POU蛋白Brn-3a的mRNA转录水平的影响

Effect of rat prenatal lead exposure on the gene transcription level of POU-domain protein Brn-3a of offspring brain

目的探讨铅对大鼠中枢神经系统神经细胞内转录因子Brn-3a基因mRNA转录水平的影响。方法雌性大鼠经围产期饮水染铅(对照组蒸馏水、低铅组0.5g/L、中铅组1.0g/L、高铅组2.0g/L)后,对其21日龄仔鼠不同脑区的Brn-3a mRNA基因转录水平进行了观察,采用逆转录酶-聚合酶链反应(RT-PCR)和组织原位杂交半定量检测Brn-3a的mRNA水平。结果RT-PCR凝胶成像系统结果显示,各染铅剂量组脑组织海马区扩增产物的电泳条带密度与对照组相比差异有显著性(P<0.05),皮层及小脑部位与对照组相比差异无显著性。原位杂交检测Brn-3a的mRNA图像分析结果显示,高铅组与对照组相比,在大脑皮层和海马部位可见平均灰度值升高(P<0.05),表明mRNA的表达量减弱,而小脑部位未见明显变化。在海马部位还可见阳性面积比显著下降(P<0.01)。结论结果表明,仔鼠大脑海马区Brn-3a基因转录水平有所下降,Brn-3a作为转录调节因子参与了铅对学习记忆损害的神经毒性过程。

Objective To explore rat prenatal lead exposure on gene transcription level of Brn-3a mRNA in the neurons of central nervous system. Methods The pregnant rats were randomly divided into 4 groups, which were provided with distilled water and contenting 0. 5g/L, 1.0g/L and 2.0g/L lead acetate solution drinking water respectively, the leadexposed period for exposure groups were limited from the 15th day after pregnancy to the 21st day when the offspring began to weaned, Brn-3a mRNA transcription level were observed by polymerase chain reaction （RT-PCR） and in situ hybridization. Results The RT-PCR results showed that Brn-3a mRNA transcription level significantly decreased in neural cells from cerebral hippocampus in all lead treatment groups compared with the control group（ P 〈 0.05）, but in cerebral cortex and cerebellum, we had not seen the same result. The in situ hybridization results showed that Brn-3a mRNA transcription level significantly decreased in high dose lead group in cerebral cortex and cerebellum（ P 〈 0.05 or P 〈 0.01 ）. Conclusion The study indicated that Brn-3a mRNA transcription level significantly decreased in neural cells from cerebral hippocampus. It might participate in the neurological toxicity as a transcription regular factor damaging the learning and memory ability induced by lead.