摘要
目的:探索齐多夫定(AZT)对造血干细胞(HSCs)自我更新相关信号通路PI3K/Akt/mTOR和相关分子Bmi-1表达的影响。方法:采用AZT干预Balb/c孕小鼠,AZT剂量分别为5.0mg/d/只和10.0mg/d/只,暴露时间为孕期第10天至分娩;取新生鼠骨髓细胞,Ficoll分离后,采用qPCR与western bloting方法检测PI3K/Akt/mTOR和相关分子Bmi-1、PTEN的表达变化。对照组分别为正常新生鼠组、成年小鼠组和老年小鼠组。结果:AZT 10.0 mg组和AZT 5.0 mg组的PI3K/Akt/mTOR信号通路中,mTOR水平表达有升高趋势,与成年小鼠组比较无明显区别,但明显低于老年小鼠组(P<0.05),而PTEN基因的表达无明显变化;Bmi-1基因表达水平较正常组和成年小鼠组高(P<0.05),但明显低于老年小鼠组(P<0.05)。AZT 10.0mg组和AZT 5.0mg组P70S6、4EBP1D较正常组升高但低于老年小鼠组(P<0.05),老年小鼠组上述蛋白表达低于正常组和成年小鼠组(P<0.05)。结论:AZT对新生鼠HSCs自我更新相关信号通路关键分子mTOR与Bmi-1存在有限影响,仍可维持在较为正常的调控水平。
Objective:To investigate the regulation of self-renewal signaling pathway PI3K-AKT-mTOR and related factor Bmi-1 expression in hematopoietic stem/progenitor cells(HSCs)in newborns of pregnancy mice exposed to zidovudine(AZT).Methods:The pregnancy Balb/c mice were exposed to AZT with the dose of 5.0 mg/day and 10.0 mg/day,exposure periods,from the 10 th day of pregnancy to birth.The offspring HSCs of bone marrows were isolated by Ficoll.The self-renewal signaling pathways PI3K/Akt/mTOR,Bmi-1 and PTEN expressions were measured by qPCR and western blot,respectively.In addition,normal newborn mice,adult mice and aged mice were served as the control group.Results:The expression of mTOR in mice exposed to AZT was increased,which was similar to that of adult mice,but lower than the old mice(P<0.05).The PTEN gene expression remained unchanged.Bmi-1 expression level was higher in mice exposed to AZT than that in the normal newborn mice and adult mice,but was significantly lower than the old mice(P<0.05).The protein expression levels above in newborn mice exposed to AZT were lower than those in adult mice and aged mice(P<0.05).Conclusion:AZT exerts limited effect on key factors in the self-renewal signaling pathway in neonatal mice.
作者
陈悦
罗敏玲
李慕军
曾雅畅
蒙春莲
邝晓聪
Chen Yue;Luo Minling;Li Mujun;Zeng Yachang;Meng Chunlian;Kuang Xiaocong(Department of Obstetrics and Gynecology,The First Affiliated Hospital of Guangxi Medical University,Nanning 530021,China;Department of Obstetrics and Gynecology,The 4th People’s Hospital,Nanning 530023,China;School of Basic Medicine,Guangxi Medical University,Nanning 530021,China)
出处
《广西医科大学学报》
CAS
2018年第4期463-467,共5页
Journal of Guangxi Medical University
基金
广西卫计委重点课题资助项目(No.桂卫重2010007)
