生命早期PM_(2.5)暴露对子代雄性大鼠前额皮层的影响

Effects of early life PM_(2.5) exposure on prefrontal cortex of offspring male rats

目的:探究生命早期不同阶段PM_(2.5)暴露对子代大鼠前额皮层的影响。方法:将12只受孕后的SD孕鼠按体重随机分为对照组(CG)、母亲孕期暴露组(MG)、出生早期暴露组(EP)和全围产期暴露组(PP),每组3只。进行孕鼠与子鼠的清洁空气或8倍浓缩PM_(2.5)的暴露,其中CG组全程不暴露,MG组从妊娠第1日(GD1)暴露到GD21,EP组从出生第1日(PND1)暴露到PND21,PP组从GD1一直暴露到PND21。暴露完成后,取各组6只子代大鼠的前额皮层,采用HE染色进行病理学检测;酶联免疫吸附实验(ELISA)进行神经炎性因子检测;高效液相色谱-质谱分析进行神经递质检测;免疫印迹实验(Western blot)进行星形胶质细胞标志物检测;比色法进行脑组织氧化应激检测。结果:与MG组和CG组子鼠比较,PP组和EP组子鼠前额皮层的病理学变化更加明显。与MG组和CG组子鼠比较,PP组和EP组大鼠的神经炎性因子IL-1、IL-6和TNF-α均显著增加(P<0.01),且MT水平显著减少(P<0.05),OT水平呈现下降趋势;神经递质Ach水平也显著增加(P<0.01)。与MG组和CG组子鼠比较,PP组和EP组子鼠的GFAP水平呈升高趋势。与MG组和CG组子鼠比较,PP组和EP组子鼠的氧化应激指标SOD水平显著减少(P<0.01),ROS水平显著增加(P<0.01)。与CG组子鼠比较PP组子鼠的CAT水平显著减少(P<0.01),与MG组子鼠比较PP组子鼠的CAT水平显著减少(P<0.05);与CG组子鼠比较EP组子鼠的CAT水平显著减少(P<0.05)。尚未发现PP组子鼠与EP组子鼠之间、MG组子鼠与CG组子鼠之间在IL-1、IL-6、TNF-α、MT、OT、Ach、GFAP、SOD、ROS和CAT水平存在差异。结论:生命早期PM_(2.5)暴露可对子代雄性大鼠前额皮层产生不良影响,出生早期暴露可能更为敏感。

Objective:To investigate the effects of PM_(2.5)exposure at different stages of early life on the prefrontal cortex of offspring rats.Methods:Twelve pregnant SD rats were randomly divided into four groups:Control group(CG),Maternal pregnancy exposure group(MG),Early postnatal exposure group(EP)and Perinatal period exposure group(PP),3 rats in each group.The pregnant and offspring rats were exposed to clean air or 8-fold concentrated PM_(2.5).MG was exposed from gestational day(GD)1 to GD21.EP was exposed from postnatal day(PND)1 to PND21,and PP was exposed from GD1 to PND21.After exposure,the prefrontal cortex of 6 offspring rats in each group was analyzed.HE staining was used to observe the pathological damage in the prefrontal cortex.ELISA was employed to detect neuroinflammatory factors,and HPLC/MSC was applied to determine neurotransmitter content.Western blot and colorimetry were applied for detecting astrocyte markers and oxidative stress markers,respectively.Results:Compared with MG and CG,the pathological changes of prefrontal cortex in PP and EP were more obvious.Compared with MG and CG,the neuroinflammatory factors(IL-1,IL-6,TNF-α)in PP and EP were increased significantly(P<0.01),the level of MT were decreased significantly(P<0.05),and the level of oxytocin(OT)showed a downward trend;the level of neurotransmitter ACh was also increased significantly(P<0.01).Compared with MG and CG,the GFAP level of PP and EP showed an upward trend,the level of oxidative stress index SOD in PP and EP was decreased significantly(P<0.01),and the level of ROS was increased significantly(P<0.01).Compared with the offspring rats of CG and MG,the CAT level of PP was decreased significantly(P<0.01,P<0.05).Compared with the offspring rats of CG,the CAT level of EP was decreased significantly(P<0.05).There was no significant difference in IL-1,IL-6,TNF-α,MT,OT,ACh,GFAP,SOD,ROS and CAT levels between PP and EP,or MG and CG.Conclusion:PM_(2.5)exposure in early life has adverse effects on the prefrontal cortex of offspring male rats,and early birth exposure may be more sensitive.