内质网应激参与双酚A导致小鼠的肝脏脂质沉积

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

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,RTPCR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、e IF2α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-e IF2α/e IF2α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。

Objective To investigate the role of endoplasmic reticulum stress （ERS） in hepatic lipid deposition in- duced by bisphenol A（BPA）. Methods Male CD1 mice were randomly divided into two groups：control group （n = lO）and BPA group（n = 10）. Mice fed with BPA [500 pLg/（kg · d） in BPA group for 8 weeks. The content of hepatic triglyceride （TG）was measured by enzyme assay kit and oil red O staining was used to determine the he- patic lipid accumulation. The mRNA level of fatty acid synthase （FAS） and fatty acid transport protein 1 （ FATP1 ） was determined by RT-PCR. Western blot was used to detect the protein expression of ERS associated proteins （ Bip, p-IRElcx/IRElcc, p-PERK/PERK, p-eIF2cc/eIF2a and SREBP- 1 c ）. 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 level of FAS and FATP1 was higher in BPA group than those in control group （P 〈 0.05 ）. The protein expression of Bip, Bip、p-IRE1α/IRE1α、p-PERK/PERK、p-e IF2α/e IF2αin BPA group was also significantly higher than control group （ P 〈 0.05 ）. Conclusions ERS maybe involved in hepatic lipid deposition of mice induced by BPA.