Dysregulation of miRNA regulatory networks by chronic ethanol consumption impairs liver regeneration

In this study, we elucidated the role of miRNA dysregulation in liver regeneration after partial hepatectomy (PHx) in chronic ethanol-treated rats. Male Sprague-Dawley rats were fed a liquid diet containing 36% of total calories derived from ethanol for 5 weeks; corresponding pair-fed calorie-matched controls were fed diets in which ethanol calories were replaced by carbohydrate. After 5 weeks, locked nucleic acid (LNA)-modified oligo antisense to miR-21 (AM21, Exiqon) was used to inhibit miRNA in vivo, and rats were subjected to 70% PHx. Liver samples were collected at 6 h, 24 h and 72 h after the surgery. The excised liver samples at t=0 served as within-animal controls.NanoString rat miRNA panel was used to obtain miRNA expression profile from 48 liver samples.本研究阐明了慢性乙醇暴露大鼠部分肝切除术（PHx）后微小RNA（miRNA）表达失调在肝再生中的作用。实验将雄性斯普拉格-道利（SD）大鼠饲喂以乙醇供能占总热量36%的液态饲料，持续5周；同期配对喂养的热量匹配对照组大鼠，则饲喂以碳水化合物替代乙醇供能的等热量饲料。造模5周后，采用针对miR-21的锁核酸（LNA）修饰反义寡核苷酸（AM21，Exiqon）进行体内miRNA抑制处理，随后对大鼠实施70%体积的部分肝切除术。分别于术后6 h、24 h和72 h采集肝组织样本；以t=0时间点（手术即刻）切除的肝组织样本作为动物内参对照。本研究采用NanoString大鼠miRNA检测面板获取了48份肝组织样本的miRNA表达谱。