铁过载通过非氧化应激依赖miR-122下调引起肝脏脂肪蓄积

IRON OVERLOAD INDUCES HEPATIC LIPID ACCUMULATION THROUGH DOWN REGULATING MIR-122 EXPRESSION INDEPENDENTLY OF OXIDATIVE STRESS

目的 探讨氧化应激及miR-122下调在右旋糖酐铁过载导致肝脏脂肪蓄积中的作用。方法 将小鼠随机分为4组。对照组小鼠腹腔注射200mg/kg右旋糖酐,另3组小鼠腹腔注射200mg/kg右旋糖酐铁构建铁过载小鼠模型,同时其中两组铁过载小鼠分别灌胃300mg/kg原花青素或槲皮素。利用试剂盒检测右旋糖酐铁过载导致肝脏损伤(血清谷丙转氨酶、谷草转氨酶,肝脏切片苏木精-伊红染色),肝脏脂肪蓄积(血清甘油三脂、总胆固醇、高密度脂蛋白、低密度脂蛋白,肝脏切片油红O染色),氧化应激(血清谷胱甘肽、丙二醛)指标。另外利用转铁蛋白结合铁(holo-Tf)处理Huh7细胞24h构建体外铁过载模型。利用PCR检测miR-122及其潜在靶基因乙酰乙酰辅酶A合成酶(AACS)在体内外铁过载模型表达变化情况。结果 原花青素或槲皮素减轻右旋糖酐铁过载引起的氧化应激,但不能减轻肝脏损伤、肝脏脂肪蓄积。PCR结果表明右旋糖酐铁过载引起miR-122下调,AACSmRNA上调,且不受氧化应激调控。结论铁过载可能通过非氧化应激依赖miR-122下调导致肝脏脂肪代谢紊乱。[营养学报,2022,44(2):182-187]

Objective To investigate the roles of oxidative stress and down-regulated miR-122 in iron overload-induced hepatic lipid accumulation. Methods Mice were randomly divided into four groups. The control group mice were intraperitoneally given 200mg/kg dextran and mice in three iron overload groups were intraperitoneally given 200mg/kg iron dextran. Two of iron overload groups were intragastrically given 300 mg/kg proanthocyanidins or quercetin respectively.Next, we detected the liver injury indexes(serum alanine aminotransferase, aspartate aminotransferase and liver section hematoxylin-eosin staining), the liver lipid-accumulating indexes(serum triglyceride, high-density lipoprotein, low-density lipoprotein and liver section oil red O staining), and the oxidative stress indexes(serum glutathione, malondialdehyde).Additionally, Huh7 cells were treated by holo-Tf for 24h as an in vitro iron overload model. The expression of miR-122 and its potential target acetoacetyl-CoA synthetase(AACS) were determined in iron overload models both in vivo and in vitro.Results Proanthocyanidins or quercetin alleviated oxidative stress induced by iron dextran overload, but had no obviously beneficial effect on liver injury and hepatic lipid accumulation. The results of PCR showed iron overload decreased miR-122expression and further increased AACS mRNA expression and proanthocyanidins or quercetin did not impact significantly on the expression of miR-122 and AACS. Conclusion Iron overload probably induced hepatic lipid accumulation through miR-122/AACS in an oxidative stress independent manner. [ACTA NUTRIMENTA SINICA, 2022, 44(2):182-187]