目的：探索母代高脂饮食对子鼠早期肝脏病理改变的影响及其可能机制。方法 SD雌性大鼠随机分成高脂饮食组(HF组)和对照组，至交配怀孕产仔，哺乳期母鼠继续原饮食并喂养子鼠至其3周龄，取子鼠肝脏组织，观察肝脏病理变化，并检测肝脏内过氧化物酶体增殖物激活受体α(PPARα)、长链脂酰辅酶A合成酶3(ACSL3)、肉毒碱棕榈酰基转移酶1α(CPT-1α)及3-羟基酰基辅酶A脱氢酶(Ehhadh)的基因表达变化。结果 HF组母鼠所育的子鼠3周龄时肝细胞胞浆内可见弥漫性空泡变性，小叶内可见点灶状坏死；HF组子鼠肝脏组织PPARα和Ehhadh基因表达水平明显高于对照组，而ACSL3基因表达则显著低于对照组，差异均有统计学意义(P<0.05)；CPT-1α基因表达水平亦高于对照组子鼠，但两组间差异无统计学意义(P=0.19)。结论母鼠孕期持续至哺乳期的高脂饮食可引起子代早期肝内脂肪酸β氧化相关基因PPARα，CPT1α与Ehhadh表达代偿性增加，ACSL3表达降低，但尚不能逆转子代肝脏脂肪变性的发生。%Objective To study the impact of maternal high-fat diet during pregnancy and lactation on hepatic steatosis in the early life of offspring rats and its possible mechanism. Methods Female Sprague-Dawley rats were fed either a high fat diet (HF) or control (C) diet for 8 weeks before mating and throughout gestation and ifrst 3 weeks of lactation. The expressions of hepatic fatty acid catabolism related genes, including peroxisome proliferator-activated receptor alpha (PPARα), acyl-CoA syn-thease long-chain family member3 (ACSL3), carnitine palmitoyltransferase-1α(CPT-1α) and 3-hydroxyacyl CoA dehydrogenase (Ehhadh) were determined in offspring liver tissue. The liver pathology was examined in offspring rats at 3 weeks of age. Results Pathohistological ifndings at 3 weeks of age showed that there were diffuse vacuolar degeneration in cytoplasm of hepatocytes and spot necrosis in hepatic lobular in the HF offspring liver. The mRNA expressions of PPARαand Ehhadh genes were markedly increased in the HF offspring as compared to the control group (P<0.05). The mRNA expression of CPT-1αgene was also higher in the HF offspring than that in control group (P=0.19). The level of ACSL3 gene expression, however, was markedly decreased (P<0.05). Conclusions Maternal high fat diet during pregnancy and lactation could result in an increased expression of genes related to hepatic fatty acidβ-oxidation, including PPARα, CPT1αand Ehhadh, but the liver steatosis cannot be reversed in the early life of offspring.
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