Department of Endocrinology, Hebei General Hospital, Shijiazhuang, China; Hebei Key Laboratory of Metabolic Diseases, Hebei General Hospital, Shijiazhuang, China.
Department of Endocrinology, Hebei General Hospital, Shijiazhuang, China; Hebei Key Laboratory of Metabolic Diseases, Hebei General Hospital, Shijiazhuang, China.
Life Sci. 2020 Sep 15;257:118090. doi: 10.1016/j.lfs.2020.118090. Epub 2020 Jul 14.
This study aimed to investigate oxymatrine via regulating miR-182 improved the hepatic lipid accumulation in non-alcoholic fatty liver disease (NAFLD) model.
Wistar rats were fed high-fat and high-fructose diet (HFDHFr group) for 4 weeks and HepG2 cells were treated with palmitic acid (PA group), and then were given oxymatrine intervention. The expression profiles of miRNAs were accessed by RNA sequencing (RNA-Seq). Hematoxylin-eosin (HE) staining and Oil Red O staining were used to observe the inflammation and lipid accumulation in liver. The levels of sterol regulatory element binding protein-1c (SREBP-1c), acetyl-CoA carboxylase (ACC), fatty-acid synthase (FAS) and carnitine palmitoyltransferase 1A (CPT-1A) were detected by RT-qPCR and Western blotting, respectively. Cell viability was detected by Cell Counting Kit-8 (CCK-8).
miR-182 was down-regulated in the HFDHFr group and PA group. Oxymatrine reduced body weight, and improved glucose tolerance and insulin resistance in the HFDHFr + OMT group compared with HFDHFr group. In addition, oxymatrine reduced the ratio (liver weight/body weight), the content of triglycerides (TG), hepatic lipid accumulation and steatosis. The levels of SREBP-1c, ACC, and FAS were significantly decreased, while the CPT-1A level was obviously elevated after oxymatrine intervention (P < 0.05). In vivo, miR-182 knockdown increased the levels of SREBP-1c, ACC and FAS, while reduced the CPT-1A level. Additionally, oxymatrine attenuated the effects of miR-182 inhibitor on lipid accumulation.
We presented a possible mechanism that oxymatrine alleviated hepatic lipid metabolism via regulating miR-182 in NAFLD model.
本研究旨在探讨氧化苦参碱（OMT）通过调节 miR-182 改善非酒精性脂肪性肝病（NAFLD）模型中的肝脂质堆积。
Wistar 大鼠给予高脂高果糖饮食（HFDHFr 组）4 周，HepG2 细胞用棕榈酸（PA 组）处理，然后给予氧化苦参碱干预。采用 RNA 测序（RNA-Seq）检测 miRNA 的表达谱。苏木精-伊红（HE）染色和油红 O 染色观察肝内炎症和脂质堆积。实时定量 PCR（RT-qPCR）和 Western blot 分别检测固醇调节元件结合蛋白-1c（SREBP-1c）、乙酰辅酶 A 羧化酶（ACC）、脂肪酸合酶（FAS）和肉碱棕榈酰转移酶 1A（CPT-1A）的水平。采用细胞计数试剂盒-8（CCK-8）检测细胞活力。
HFDHFr 组和 PA 组 miR-182 表达下调。与 HFDHFr 组相比，HFDHFr+OMT 组氧化苦参碱降低了体重，改善了葡萄糖耐量和胰岛素抵抗。此外，氧化苦参碱降低了肝重/体重比、三酰甘油（TG）含量、肝脂质堆积和脂肪变性。SREBP-1c、ACC 和 FAS 的水平显著降低，而 CPT-1A 水平明显升高（P<0.05）。在体内，miR-182 敲低增加了 SREBP-1c、ACC 和 FAS 的水平，同时降低了 CPT-1A 水平。此外，氧化苦参碱减弱了 miR-182 抑制剂对脂质堆积的影响。
我们提出了一种可能的机制，即氧化苦参碱通过调节 miR-182 减轻 NAFLD 模型中的肝脂质代谢。
