基础医学与临床 ›› 2016, Vol. 36 ›› Issue (7): 886-890.

• 研究论文 • 上一篇    下一篇

内质网应激参与双酚A导致小鼠的肝脏脂质沉积

李丹婷,刘露路,高茹菲,彭川,杨淑敏,胡金波,肖晓秋,李启富   

  1. 重庆医科大学附属第一医院
  • 收稿日期:2015-10-09 修回日期:2015-12-02 出版日期:2016-07-05 发布日期:2016-06-22
  • 通讯作者: 李启富 E-mail:liqifu@yeah.net
  • 基金资助:
    从构筑转录因子HMGA2在胃癌中的调控网络探讨上皮间质转化和肿瘤细胞干性获取之间的关系;国家临床重点专科建设项目

Endoplasmic reticulum stress is involved in bisphenol A-induced hepatic lipid deposition of mice

  • Received:2015-10-09 Revised:2015-12-02 Online:2016-07-05 Published:2016-06-22
  • Supported by:
    ;National Key Clinical Specialties Construction Program of China (No. [2013]544)

摘要: 目的 研究内质网应激在双酚A(BPA)导致的肝脏脂质沉积中的作用。方法 将雄性CD1小鼠随机分为对照组(n = 10)和BPA组(n = 10)。BPA组给予一定浓度BPA的饲料进行喂养[BPA质量按照500μg/(kg?d)的量加入普通饲料]。8周后化学酶促-比色法检测肝脏三酰甘油(TG)含量,油红O染色观察肝脏内脂质聚集情况,RT-PCR法检测肝脏组织脂肪酸合成酶(FAS)和脂肪酸转运蛋白1(FATP1)的mRNA表达。Western blot检测内质网应激相关蛋白(Bip、IRE1α、PERK、eIF2α和SREBP-1c)等蛋白及其磷酸化的表达水平。 结果 与对照组相比,BPA组小鼠肝脏的TG含量明显增加(P < 0.05);油红O染色结果与TG定量一致。BPA组肝脏组织中FAS和FATP1的mRNA表达水平显著高于对照组(P < 0.05)。BPA组肝脏组织中Bip、p-IRE1α/IRE1α、p-PERK/PERK、p-eIF2α/eIF2α和SREBP-1c的蛋白表达水平显著高于对照组(P < 0.05)。结论 内质网应激途径可能参与了BPA所导致的肝脏脂质沉积。

关键词: 双酚A, 脂质沉积, 内质网应激

Abstract: Objective To investigate the role of endoplasmic reticulum stress(ERS)in hepatic lipid deposition induced by bisphenol A(BPA). Methods Male CD1 mice were randomly divided into two groups:control group (n = 10)and BPA group(n = 10). Mice fed with BPA [500μg/(kg?d)] in BPA group for 8 weeks. The content of hepatic triglyceride(TG)was measured by enzymic assay kit and oil red O staining was used to determine the hepatic lipid accumulation. The mRNA levels of fatty acid synthase(FAS)and fatty acid transport protein 1(FATP1)were determined by RT-PCR. Western blot was used to detect the protein expression levels of ERS associated proteins(Bip、p-IRE1α/IRE1α、p-PERK/PERK、p-eIF2α/eIF2α and SREBP-1c). Results Compared with control group ,the level of TG was higher in BPA group(P < 0.05). Oil red O staining also revealed that BPA promoted hepatic lipid accumulation. The mRNA levels of FAS and FATP1 were higher in BPA group than those in control group(P < 0.05). The protein expression levels of Bip、p-IRE1α/IRE1α、p-PERK/PERK、p-eIF2α/eIF2α and SREBP-1c in BPA group were also significantly higher than control group (P < 0.05). Conclusion ERS could be involved in hepatic lipid deposition of mice induced by BPA.

Key words: bisphenol A, lipid deposition, endoplasmic reticulum stress