| 于俊杰,詹晓蓉,王晓辰,李新宇,刘晓民.MicroRNA-185改善非酒精性脂肪肝小鼠胰岛素敏感性并调节脂代谢基因的表达[J].,2018,(8):1425-1430 |
| MicroRNA-185改善非酒精性脂肪肝小鼠胰岛素敏感性并调节脂代谢基因的表达 |
| MicroRNA-185 Improves Insulin Sensitivity and Regulates Expression of Lipid Metabolism Genes in Mice with Non-alcoholic Fatty Liver Disease |
| 投稿时间：2017-08-23 修订日期：2017-09-20 |
| DOI：10.13241/j.cnki.pmb.2018.08.005 |
| 中文关键词: miR-185 非酒精性脂肪性肝病 脂质代谢 胰岛素信号通路 |
| 英文关键词: miR-185 Nonalcoholic fatty liver disease Lipid metabolism Insulin signaling pathway |
| 基金项目:国家自然科学基金项目（30950005） |
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| 中文摘要: |
| 摘要 目的：探讨microRNA-185(miR-185)对高脂饮食的小鼠模型的HepG2肝细胞脂质代谢和胰岛素信号通路的调节作用。方法：应用定量反转录聚合酶链反应评估过表达或抑制miR-185表达脂质合成相关基因的mRNA水平。此外，应用Western Blot方法测定转染HepG2细胞pre-mir-185后的关键信号通路组分(IRS-1，IRS-2，PI3K、AKT2)和磷酸化PI3K 和AKT2的表达情况。结果：诱导的人类HepG2细胞的软脂酸对mir-185水平的下降具有时间和剂量依赖性。经过mir-185转染的HepG2细胞显著降低脂肪酸合成酶，3-hydroxy-3-methylglutaryl-coa还原酶，固醇调节元件结合蛋白和固醇调节元件结合蛋白-1c 的mRNA水平，而使用anti-mir-185寡核苷酸抑制mir-185在HepG2细胞中产生相反的作用。在高脂饮食的小鼠模型，与对照组动物相比，mir-185处理后脂质积累明显改善。mir-185诱导后通过上调胰岛素受体底物2增强胰岛素信号通路。结论：miR-185在体内和体外调节肝细胞脂肪酸代谢和胆固醇平衡，以及在改善胰岛素敏感性中起重要作用，miR-185可能成为非酒精性脂肪肝和胰岛素抵抗的新靶点和治疗非酒精性脂肪肝药物作用新靶标。 |
| 英文摘要: |
| ABSTRACT Objective: To investigate the effects of microrna-185 (miR-185) on lipid metabolism and insulin signaling pathway in human HepG2 liver cells in a high-fat diet mouse model. Methods: quantitative reverse transcription polymerase chain reaction was used to evaluate overexpression or inhibition of miR-185 expression in lipid synthesis related genes at mRNA levels. In addition, the critical signaling pathway components (IRS-1, IRS-2, PI3K, AKT2) and phosphorylated PI3K and AKT2 were measured by Western Blot assay after transfection of HepG2 pre-mir-185 cells. Results: miR-185 levels decreased in time and in response to the dose dependence of palmitic acid in HepG2 hepatocytes. With miR-185 transfected HepG2 cells significantly decreased the level of mRNA 3-hydroxy-3-methylglutaryl-CoA reductase of fatty acid synthase, sterol regulatory element binding protein and sterol regulatory element binding protein -1c, and inhibition of miR-185 produced the opposite effect using anti-miR-185 oligonucleotides in HepG2 cells. In a high-fat diet mouse model, mir-185 improved significantly after lipid accumulation, compared with controls. Induction of miR-185 enhances insulin signaling pathways by up regulation of the insulin receptor substrate -2. Induction of miR-185 enhances insulin signaling pathways by up regulation of the insulin receptor substrate -2. Conclusion: These results suggest that MiR-185 plays an important role in regulating fatty-acid metabolism and cholesterol homeostasis in hepatocytes，as well as improving insulin sensitivity in vitro and in vivo. MiR-185 may be a new target for nonalcoholic fatty liver disease and insulin resistance and a new drug target for the treatment of nonalcoholic fatty liver disease. |
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