双酚A对小鼠睾丸间质细胞毒性及miR-203-3p和PI3K/AKT/FOXO1信号通路的影响

Effects of bisphenol A on the toxicity and miR-203-3p and PI3K/AKT/FOXO1 signaling pathway in Leydig cells of mice

目的研究双酚A对小鼠睾丸间质细胞的毒性作用,及对miR-203-3p和PI3K/AKT/FOXO1信号通路的影响。方法不同浓度BPA(0、2、10、50、250μmol/L)处理小鼠睾丸间质细胞24 h,CCK8法检测细胞活力,Real time PCR检测miR-203-3p和FOXO1、AKT、PI3K的相对表达水平。结果不同浓度BPA处理细胞后,细胞活力随BPA剂量的增大而减少,50、250μmol/L组与对照组比较,差异有统计学意义(P<0.001)。各处理组miR-203-3p表达量均较对照组升高,10、250μmol/L组与对照组比较,差异有统计学意义(P<0.05)。2、10μmol/L组FOXO1表达量较对照组升高,50、250μmol/L组表达量较对照组降低,2、50、250μmol/L组FOXO1相对表达量与对照组比较差异有统计学意义(P<0.001)。各处理组AKT水平均出现下降趋势,10、50、250μmol/L组与对照组比较,差异有统计学意义(P<0.001)。各处理组PI3K水平均出现下降趋势,50、250μmol/L组与对照组比较,差异有统计学意义(P<0.001)。结论双酚A致睾丸间质细胞损伤,影响miR-203-3p和FOXO信号通路相关基因的改变。

Objective To investigate the toxic effect of bisphenol A(BPA)on Leydig cells of mice and its effect on miR-203-3 p and PI3 K/AKT/FOXO1 signaling pathway.Methods Different concentrations of BPA(0,2,10,50,250μmol/L)were used to treat the Leydig cells of mice for 24 hours.CCK8 method was used to detect the cell viability.Real time PCR was used to detect the relative expression levels of miR-203-3 p and FOXO1,AKT and PI3 K.Results After treatment with different concentrations of BPA,the cell viability decreased with the increase of BPA dosage.The difference between 50 and 250μmol/L groups and control group was statistically significant(P<0.001).The expression of miR-203-3 p in each treatment group was higher than that in control group,and the difference between 10 and 250μmol/L groups and control group was statistically significant(P<0.05).The expression of FOXO1 in 2 and 10μmol/L groups was higher than that in control group,while that in 50 and 250μmol/L groups was lower than that in control group.The difference in relative expression of FOXO1 between 2,50 and 250μmol/L groups and control group was statistically significant(P<0.001).The AKT level of each treatment group showed a downward trend,and the difference was statistically significant between 10,50 and 250μmol/L groups and control group(P<0.001).The level of PI3 K in each treatment group showed a downward trend,and the difference between the 50 and 250μmol/L groups and the control group was statistically significant(P<0.001).Conclusion BPA can damage the Leydig cells and affect the changes of the related genes of miR-203-3 p and FOXO signal pathway.