【摘要】 目的研究母鼠围生期经饮水摄入低剂量双酚A(BPA)对子代芳香烃受体(AHR)和辅助性T(Th)17细胞的影响。方法将确认妊娠的ICR母鼠随机分成空白对照组和溶剂对照组、10、100和1 000 nmol/L BPA组;母鼠自妊娠第0天(GD 0)至仔鼠出生后第21天(PND 21)经饮水摄入BPA。PND 21时处死仔鼠,取血用ELISA法测血清白细胞介素(IL)-17和IL-23含量,取脾脏,流式细胞术检测Th17细胞比例,实时荧光定量聚合酶链反应(RT-q PCR)检测维甲酸相关孤核受体γt(RORγt)和AHR mRNA表达水平。结果与空白对照组比较,各BPA剂量组母鼠孕期体重、仔鼠出生和PND 21时体重、窝仔数差异均无统计学意义;100和1 000 nmol/L BPA组仔鼠PND 21时脾脏Th17细胞比例均显著升高(P<0.05),脾脏RORγt mRNA和AHR mRNA表达水平明显上调(P<0.01),血清IL-17和IL-23含量也明显上升(P<0.01);脾脏Th17细胞比例和RORγt mRNA表达水平与AHR mRNA表达水平均呈正相关性(P<0.01)。结论围生期母鼠暴露于低剂量BPA可导致子代断乳时AHR表达上调,并经RORγt途径促进Th17细胞发育。更多还原

【Abstract】 Objective The present study was to investigate the effects of low- dose bisphenol A( BPA) exposure by drinking water during perinatal period on aryl hydrocarbon receptor( AHR) and Th17 cells in its offspring.Methods The pregnant ICR mice were randomly divided into 5 groups: blank control,vehicle control,10,100 and 1 000 nmol / L BPA groups and exposed to BPA by drinking water from gestational day 0( GD 0) to postnatal day 21( PND 21). Fetuses were sacrificed on PND 21. The levels of IL-17 and IL-23 in serum were detected by ELISA,and the proportion of Th17 cells in spleen was measured by flow cytometry. RT-q PCR was conducted to detect the mRNA levels of RORγt and AHR in spleen. Results As compared to the control group,the maternal body weight during pregnancy,fetal body weight at birth and PND 21,the number of fetuses per litter,were all found of no significant difference in BPA groups. In fetuses at PND 21 in 100 and 1 000 nmol / L BPA groups,the proportion of Th17 cells in spleen was significantly increased( P < 0. 05); the mRNA levels of RORγt and AHR were markedly raised( P < 0. 01); meanwhile,serum IL-17 and IL-23 were significantly increased( P < 0. 01),compared with the control. A positive correlation was observed between the proportion of Th17 cells and the mRNA levels of RORγt,AHR( P < 0. 01). Conclusion Perinatal exposure of BPA at a low dose can increase the level of AHR,and promote the differentiation of Th17 cells through RORγt in offspring after weaning.更多还原