Pes1通过PI3K/AKT/GSK-3β信号通路对胆汁淤积性肝病小鼠的作用  

Effect of Pes1 on mice with cholestatic liver disease via PI3K/AKT/GSK-3β signaling pathway

作　　者：杨仁俊 汪婧[1] 孙颉 张娜[1] 孔德润[1] Yang Renjun;Wang Jing;Sun Jie(Dept of Gastroenterology,The First Affiliated Hospital of Anhui Medical University,Hefei 230022)

机构地区：[1]安徽医科大学第一附属医院消化内科

出　　处：《安徽医科大学学报》2019年第10期1511-1515,共5页Acta Universitatis Medicinalis Anhui

基　　金：国家自然科学基金(编号:81271736);2018年重点研究与开发计划项目(编号:9021240204)

摘　　要：目的探讨Pescadillo同源蛋白1(Pes1)以及PI3K/AKT/GSK-3β信号通路中的蛋白在胆汁淤积性肝病小鼠中的表达及其对疾病的影响。方法利用喂食3,5-二乙氧基羰基-1,4-二氢-2,4,6-三甲基吡啶(DDC)的C57BL/6为实验组,正常喂饲的C57BL/6为对照组。首先测试小鼠血清中生化指标的水平。Western blot法检测小鼠肝脏Pes1和磷脂酰肌醇3-激酶(PI3K)/蛋白激酶B(PKB/AKT)/糖原合酶激酶-3β(GSK-3β)信号通路中蛋白的表达,同时采用实时荧光定量PCR(RT-PCR)检测Pes1 mRNA的表达水平。结果血清中总胆汁酸(TBA)、总胆红素(TBIL)、碱性磷酸酶(AKP)、γ-谷氨酰转肽酶(GGT)水平在胆汁淤积性肝病小鼠中高于对照组。Pes1 mRNA和蛋白水平在胆汁淤积性肝病小鼠中均低于正常组小鼠,PI3K/AKT/GSK-3β信号通路中的磷酸化蛋白水平在胆汁淤积性肝病小鼠均明显低于对照组小鼠。结论Pes1在胆汁淤积性肝病小鼠中低表达,降低的Pes1使PI3K/AKT/GSK-3β信号通路失活,使其信号通路中PI3K和AKT的磷酸化蛋白水平依次降低,最终下调了磷酸化GSK-3β的表达,使磷酸化GSK-3β对肝细胞凋亡的抑制、减轻细胞损伤的作用减弱,进而加重了胆汁淤积性肝病的进程。Objective To investigate the expression of proteins in Pescadillo homologue 1(Pes1)and PI3K/AKT/GSK-3βsignaling pathways in mice with cholestatic liver disease and their effects on diseases.Methods C57BL/6 fed with 3,5-diethoxycarbonyl-1,4-dihydrocollidine(DDC)was used as the experimental group and normal C57BL/6 was used as the control group.The level of biochemical indicators in the serum of mice were first measured.Western blot was used to detect the expression of proteins in Pes1 and protein phosphoinositide-3-kinase(PI3K)/protein kinase B(PKB/AKT)/glycogen synthase kinase 3 beta(GSK-3β)signaling pathway in mouse liver,at the same time,the level of mRNA expression of the Pes1 was detected by Real time-PCR(RT-PCR).Results The levels of total bile acid(TBA),total bilirubin(TBIL),alkaline phosphatase(AKP)andγ-glutamyltranspeptidase(GGT)in serum were higher in the mice with cholestatic liver disease than that in the control group.The levels of Pes1 mRNA and protein were lower in the mice with cholestatic liver disease than those in the control group.The phosphorylated protein levels in the PI3K/AKT/GSK-3βsignaling pathway were significantly lower in the mice with cholestatic liver disease mice than those in the control group.Conclusion Pes1 is lower expression in mice with cholestatic liver disease,and decreased Pes1 inactivates the PI3K/AKT/GSK-3βsignaling pathway,which leads to a decrease in phosphorylated protein levels of PI3K and AKT in the signaling pathway.Finally,the expression of phosphorylated GSK-3βis down-regulated,and the inhibitory effect of phosphorylated GSK-3βon hepatocyte apoptosis and the reduction of cell damage is attenuated,thereby aggravating the progression of cholestatic liver disease.

关 键 词：Pes1 胆汁淤积性肝病 DDC模型小鼠 PI3K/AKT/GSK-3β信号通路 

分 类 号：R575.7[医药卫生—消化系统]