PPAR $ \beta $ 对双酚 A 诱导的小鼠肝脏脂质代谢紊乱的调控

双酚A（BPA）是一种外源性内分泌干扰物，与多种代谢相关疾病密切相关，生命早期BPA暴露会导致雄性小鼠非酒精性脂肪肝（nonalcoholic fatty liver disease，NAFLD），但该效应是否具有持续的暴露依赖性尚不清楚。文章研究过氧化物酶体增殖物激活受体（peroxisome proliferators-activated receptors，PPARs）调控BPA诱导的小鼠肝脏脂质代谢紊乱的机制，选用雄性C57BL/6小鼠作为实验对象，设置对照组（生理盐水）和BPA组（BPA给药量 $ 500\mu g/(kg\cdot d) $），以灌胃方式对3周龄小鼠进行药物暴露至8周龄，随后经过56 d停药期。结果显示：BPA组小鼠肝脏出现脂质堆积，经过56 d停药期，肝脏脂质堆积得到部分缓解，但是血清检测结果显示肝脏损伤依然存在；mRNA和蛋白质印迹（Western blotting，WB）结果显示，PPARs3种亚型中的β蛋白表达显著升高，且其下游靶基因硬脂酰辅酶A去饱和酶1（stearoyl-coenzyme A desaturase 1，SCD1）、载脂蛋白D（APOD）差异性表达 $ (P<0.05) $。该研究结果表明，PPARβ参与调控BPA暴露导致的小鼠脂质代谢紊乱，停止暴露后，PPARβ上调可缓解肝脏脂质堆积的症状。

A variety of metabolism-related diseases can be induced by bisphenol A(BPA), an exogenous endocrine disruptor. The early-life BPA exposure causes nonalcoholic fatty liver disease(NAFLD) in male mice, but whether this effect has a persistent exposure dependence remains unclear. This study was conducted to investigate the mechanism of peroxisome proliferators-activated receptors(PPARs) in regulating BPA-induced hepatic lipid metabolism disorders in mice. Male C57BL/6 mice were selected as experimental subjects, and the experimental groups were set up as control group(saline) and BPA group(500 $ \mu $g/(kg·d) BPA). Drug exposure was performed in 3-week-old mice by gavage until 8 weeks of age, followed by a 56 d withdrawal period. The results showed hepatic lipid accumulation in BPA-exposed mice, which was partially relieved after a 56 d withdrawal period, but serum test results showed that liver damage still existed. The mRNA and Western blotting(WB) results showed that the $ \beta $ protein expression was significantly elevated in three isoforms of PPARs and its target genes stearoyl-coenzyme A desaturase 1(SCD1) and apolipoprotein D(APOD) were differentially expressed (P<0.05). The results showed that PPAR $ \beta $ was involved in regulating the disorders of lipid metabolism in mice caused by BPA exposure, and the upregulation of PPAR $ \beta $ alleviated the symptoms of hepatic lipid accumulation after cessation of exposure.