HNF-4α通过miR-122调节2型糖尿病肝糖异生和脂质代谢紊乱的体内外研究

来源 :中国药理学会第十三次全国学术大会 | 被引量 : 0次 | 上传用户:wzmuyelan
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  目的 探讨HNF-4α是否通过上调miR-122,进而激活2型糖尿病肝脏糖异生及脂质代谢紊乱.方法 建立2型小鼠糖尿病模型,检测2型糖尿病小鼠肝脏以及棕榈酸诱导的HepG2细胞中miR-122、HNF-4α,糖异生关键酶PEPCK和G6Pase以及脂质代谢相关蛋白SREBP、FAS-1、CPT-1、ACC的表达水平.给予HNF-4α siRNA、HNF-4α过表达质粒、HNF-4α过表达质粒联合miR-122抑制剂共同孵育干预HepG2细胞,检测各组miR-122、HNF-4α、糖异生关键酶、脂质代谢相关蛋白的表达水平.结果 miR-122在2型糖尿病小鼠肝脏和棕榈酸诱导的HepG2细胞中表达均有明显增高.HNF-4α、PEPCK、G6 Pase和SREBP、FAS-1和ACC模型组中均明显上调,而CPT-1和p-ACC表达明显下降.而miR122的抑制剂能明显逆转HNF-4α过表达质粒引起的糖异生和脂质代谢相关蛋白的改变.结论 HNF-4α能够通过上调miR-122激活2型糖尿病糖脂质代谢紊乱.
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