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. miRNA expression was profiled in chronic ethanol-fed (EtOH) and carbohydrate control pair-fed (CHO) rat liver prior to (control, t=0) and 6 h, 24 h and 72 h after 70% partial hepatectomy (PHx), or at 0 h and 24 h with AM21 treatmemt.

本研究阐明了慢性乙醇暴露大鼠部分肝切除术（Partial Hepatectomy, PHx）后miRNA（microRNA）表达失调在肝再生中的作用。将雄性斯普拉格-道利（Sprague-Dawley）大鼠喂食以乙醇供能占总热量36%的液体饲料，持续5周；同期配对喂养的热量匹配对照组大鼠，则喂食以碳水化合物替代乙醇供能热量的饲料。造模5周后，采用锁核酸（locked nucleic acid, LNA）修饰的miR-21反义寡核苷酸（AM21，Exiqon）进行体内miRNA抑制，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及72 h采集肝组织样本；术前（t=0）获取的切除肝组织样本作为个体内对照。采用NanoString大鼠miRNA检测面板对48份肝组织样本进行miRNA表达谱分析。分别对慢性乙醇喂养（EtOH）及碳水化合物配对喂养（CHO）的大鼠肝组织开展miRNA表达谱分析，采样时点涵盖术前（对照，t=0）、70%部分肝切除术后6 h、24 h及72 h，以及经AM21处理后的0 h与24 h。