【摘要】 目的 探讨BPA及其在体内的生物转化产物对大鼠肝脏糖代谢关键因子的影响。方法 将受孕的24只雌鼠随机分为对照组、BPA 80 mg/kg组，每组12只，对母鼠采用灌胃方式进行染毒，染毒容积为5 ml/kg，每天一次，从受孕第5天至仔鼠出生后第21天，共染毒37天。文献查阅选择BPA主要代谢组分，应用MOE软件将BPA的代谢组分与大鼠肝脏糖代谢关键因子进行分子对接，RT-PCR及Western Blot方法检测高评分靶点mRNA和蛋白表达情况。结果 BPA 10种谢组分中，Glu-BPA与AKT、GSK3β、GLUT4、PI3K、FOXO1对接评分最高，与对照组相比，BPA组的AKT、PI3K、GLUT4及GSK3β表达水平更低（P<0.05）。结论 BPA通过影响PI3K/AKT/GSK3β信号通路及转运蛋白GLUT4影响糖代谢；分子对接技术可以有效预测BPA代谢组分对糖代谢关键分子靶点的影响，是网络药理学方法在毒性机制研究中应用的有效尝试。更多还原

【Abstract】 Objective To understand the effects of bisphenol A(BPA)and its biotransformation products in vivo on key factors of hepatic glucose metabolism in rats. Methods Totally 24 pregnant rats were randomly divided into control and BPA(80 mg/kg) exposed groups,12 in each and the rats were treated with BPA through gavage,at the dose of 5 ml/kg,once a day,from the5th day of conception to the 21st day after birth for 37 days. Using literature review to select the main metabolic components of BPA,MOE software was applied to dock the metabolic components of BPA with the key factors of glucose metabolism in rat liver,and the mRNA and protein expression of high scoring targets were detected by RT-PCR and Western blot. Results Among 10 metabolic components of BPA,Glu BPA was correlated with Akt,GSK3 β,GLUT4,PI3K,FoxO1 had the highest scores for docking,and compared with the control group,the BPA group had higher scores for Akt,PI3K,GLUT4 and GSK3 β,the expression level significantly decreased(P <0.05). Conclusion BPA may have effect on glucose metabolism through influencing PI3K/Akt/GSK3β signaling pathway and transporter GLUT4. Molecular docking technology can effectively predict the effects of BPA metabolic components on key molecular targets of glycometabolism and is an effective attempt for the application of network pharmacology methods in the study of toxic mechanisms.更多还原