目的 研究姜黄素（curcumin,Cur）对高脂饲料喂养小鼠肝脏microRNAs（miRs）及Nrf2/Keap1、氧化还原状态、脂代谢的影响。方法 24只C57BL/6J雄性小鼠随机分为3组：对照组（NC）,高脂组（HF）,Cur组（Cur）,后两组高脂饲料喂养,Cur组同时采用200 mg/（kg·d）Cur灌胃。12 w后观察小鼠肝脏病理学形态,测定肝脏靶向Nrf2或Keap1的相关miRs、Nrf2信号通路相关基因和脂代谢相关基因的表达,以及氧化应激标志物水平。结果 与高脂组相比,Cur有效改善小鼠血脂紊乱,抑制肝脏脂肪沉积,通过下调miR-28、miR-27a和miR-34a,上调miR-200a,促进Nrf2的核内易位,上调NQO1和HO-1的表达并增加抗氧化酶GPx、SOD、CAT活性及GSH水平,降低MDA水平,下调脂质生成基因PPARγ、C/EBPα的表达,促进脂肪酸氧化相关基因PPARα、CPT1α的表达。结论 Cur通过作用于miR/Nrf2信号通路,维持肝脏氧化还原状态,调节脂代谢,预防非酒精性脂肪肝。
Abstract
Objective To study the effects of curcumin on expressions of hepatic Nrf2/Keap1-targeted microRNAs and Nrf2/Keap1, redox status, and lipid metabolism in high fat diet fed mice. Methods Twenty-four male C57BL/6J mice were randomly divided into three groups: normal control (NC) group, high fat (HF) diet fed group, high fat and curcumin (Cur) group. The mice from the Cur group were fed a high fat diet and received curcumin treatment at the dose of 200 mg/(kg·d) by oral gavage. Twelve weeks later, hepatic histology, expressions of hepatic miRs that targeted on Nrf2/Keap1, and genes in the Nrf2 signaling pathway and lipid metabolism, as well as the oxidative stress biomarkers were determined. Results Compared with the HF group, curcumin effectively improved plasma lipid profiles and inhibited hepatic fat accumulation possibly by down-regulating miR-28, miR-27a and miR-34a and up-regulating miR-200a, resulting in enhanced Nrf2 nuclear translocation and up-regulation of NQO1 and HO-1. Additionally, hepatic GPx, SOD, and CAT activities and GSH level were significantly higher in the Cur group than those in the HF group, while MDA level was remarkably lower. Curcumin also down-regulated the expressions of lipogenesis genes PPARγ and C/EBPα, and up-regulated the expressions of fatty acid oxidation genes PPARα and CPT1α. Conclusion Curcumin can prevent high fat diet induced non-alcoholic fatty liver disease by maintaining hepatic redox status and lipid metabolism via miR/Nrf2 signaling pathway.
关键词
非酒精性脂肪肝 /
姜黄素 /
microRNA /
Nrf2 /
脂代谢
Key words
nonalcoholic fatty liver disease /
curcumin /
microRNA /
Nrf2 /
lipid metabolism
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基金
国家自然科学基金（No.81703222）; 张家港青年科技计划(No.ZJGQNKJ202124)
