中文摘要：

目的通过检测胎儿宫内生长受限（intrauterine growth restriction,IUGR）子鼠肝脏中脂肪代谢关键酶及可促进脂肪合成的核转录因子固醇调节元件结合蛋白1c（SREBP1c）的表达,探讨IUGR个体发生脂肪性肝病的分子机制。方法通过孕期低蛋白饮食法复制大鼠IUGR模型,采用定量逆转录-聚合酶链反应和Western blotting技术检测孕20 d（E20）胎鼠和12周成年子鼠（A12）肝脏中SREBP1c的mRNA和蛋白含量,同时检测肝脏脂肪酸合酶（FAS）和肝脂肪酶（HL）的表达变化。结果 IUGR成年子鼠肝脏三酰甘油浓度增加（P〈0.01）。IUGR胎鼠和成年子鼠肝脏SREBP1和FAS的mRNA和蛋白表达均明显高于同龄对照,且FAS与SREBP1c的mRNA水平成正相关（均P〈0.05）。IUGR胎鼠肝脏HL表达正常但成年后表达增高（均P〈0.05）。结论 ＂胎儿程序化＂影响使IUGR子代自围产期至成年肝脏中脂肪合成的调控因子SREBP1表达增加,诱导生脂酶FAS的表达,可能是成年肝脏脂质堆积及脂肪性肝病高发的机制之一。

英文摘要：

【Objective】 To explore the molecular mechanism that intrauterine growth restriction（IUGR） programs the offspring to fatty liver later in life,we determined the expression of fat metabolism enzymes and that of the transcription factor SREBP1c which promotes lipogenesis in hepatic of IUGR rats.【Methods】 IUGR model were established by maternal protein-malnutrition.Hepatic mRNA levels and protein expression of SREBP1c,FAS and HL were measured in offsprings at E20 and A12 by QRT-PCR and Western blotting.【Results】 The liver triglyceride concentration of IUGR adult offsprings were significantly higher than that of same-aged control groups（P〈0.01）.Hepatic mRNA and protein levels of SREBP1c and FAS in IUGR animals were significantly elevated at E20 and A12 compared with control rats.（all P〈0.05）.And FAS mRNA levels were positively correlated with that of SREBP1c.No significant differences were observed in hepatic HL expression concentration at E20.By 12 weeks,IUGR rats developed higher hepatic HL expression（both P〈0.05）.【Conclusions】 These data suggest that ＂fetal programmed＂ caused increased expression of SREBP1 in the hepatic of IUGR offspings,which contributed to the increased expression levels of hepatic FAS,and subsequently promoted lipid accumulation and fatty liver later in life.