妊娠期PM2.5暴露诱导子代鼠大脑皮层中p53、c-Fos表达升高

PM_(2.5) exposure during pregnancy causes expression changes of p53 and c-Fos in the cerebral cortex of the offspring mice

目的研究妊娠期PM_(2.5)暴露后子代鼠大脑皮层凋亡相关蛋白p53和c-Fos的表达变化,探讨妊娠期PM_(2.5)暴露致子代鼠大脑皮层损伤的分子机制。方法利用气管滴注改良法,建立妊娠期小鼠PM_(2.5)暴露模型。孕鼠随机分为空白组、对照组、PM_(2.5)低、中、高剂量组。子代鼠出生后第14d,分离大脑皮层,荧光定量PCR检测凋亡相关蛋白p53和c-Fos mRNA的表达;Western blot检测p53和c-Fos蛋白的表达;免疫荧光染色检测p53和c-Fos在大脑皮层的分布。结果 PM_(2.5)中、高剂量组大脑皮层p53和c-Fos mRNA和蛋白表达较对照组明显增多,p53和c-Fos主要分布在额叶大脑皮层的锥体细胞层、内颗粒层和节细胞层。结论妊娠期PM_(2.5)暴露可导致子代鼠大脑皮层凋亡相关基因激活,这可能是PM_(2.5)致子代大脑皮层损伤发生的分子机制之一。

Objective To investigate the expression of apoptosis-related genes p53 and c-Fos in the cerebral cortex of offspring mice born of maternal mice exposed to PM2.5 during pregnancy, and to explore the molecular mechanism of cortex injury in these offspring mice. Methods The PM2.5 exposure model of pregnant mice was established by modified tracheal drip method. Pregnant mice were randomly divided into blank control group, mock-treated group and other 3 groups with low, medium and high dose of PM2.5 exposure, respectively. On the 14th day after birth, the cerebral cortex was isolated from the offspring mice, and the expression of apoptosis- related genes p53 and c-Fos mRNA was detected by fluorescence quantitative PCR;the expression of P53 and c-Fos protein was detected by Western blot;and the distribution of P53 and c-Fos in the cerebral cortex was detected by immunofluorescence staining. Results In the cerebral cortex of medium and high dose of PM2.5 exposure groups, the expression of p53 and c-Fos mRNA and protein was significantly higher than that of the control group. It showed that p53 and c-Fos were mainly distributed in the pyramidal cell layer, internal granular layer and ganglion cell layer of frontal cortex. Conclusion PM2.5 exposure during pregnancy can lead to activation of apoptosis-related genes in the cerebral cortex of offspring mice, which may be one of the molecular mechanisms of PM2.5-induced cortex injury in offspring.