术后肝再生进程中肝细胞脂肪聚积相关性基因的筛查分析

Screening and identifying genes associated with transient hepatocellular steatosis during liver regeneration after partial hepatectomy in mice

目的观察肝部分切除术（PH）后肝再生过程中肝细胞一过性脂肪聚积相关性基因的表达谱。方法小鼠随机分为70％PH组（按术后时间分为0-72h时相小组，每小组5只）和假手术组（分组同前）。不同时相点获取的肝组织分别实施油红O染色的肝细胞脂聚积分析和RNA制备。用cDNA微阵列法筛查并用实时RT-PCR确认PH组和假手术组各时相点（0-24h）生脂基因的诱导表达情况。结果与假手术组和手术组0h等时相点比较，PH后的12h和24h时相点的油红O染色明显增强。经cDNA微阵列筛查并经实时RT-PCR独立确认的、仅在PH后6h和或12h时相点诱导表达的生脂基因有：Adipsin、AP2、S3-12和FSP27。结论术后肝再生过程中，肝细胞在聚积大量脂肪之前启动了一个与脂肪聚积相关的生脂基因表达程序。

Objective To identify and confirm the pattern of gene expression induced in association with transient hepatocellular fat accumulation during liver regeneration after partial hepatectomy （PH）. Methods Mice were subjected to PH and sham surgery and their livers harvested at serial time points following surgery for oil red O （ORO） staining of fat accumulation and for RNA preparation. Microarray-based gene expression analysis of regenerating and sham operated liver from 0 to 24 h after surgery was performed to reveal induction of adipogenic gene expression. Real time RT-PCR analysis confirmed induction of adipogenic gene expression in the regenerating liver. Results ORO staining was markedly increased in regenerating liver 12-24 h after PH as compared to quiescent liver （0 h）, regenerating liver from earlier and latter time point, and sham-operated liver. Within the genes identified by microarray- based gene expression analysis as induced during liver regeneration and confirmed independently by real time RT-PCR, several adipogenic genes, such as adipsin, AP2, S3-12, and FSP27, were induced only in the regenerating liver 6 h and（or） 12 h after PH. Conclusion During liver regeneration after PH, prior to transient hepatocellular steatosis, the early regenerating liver activates a program of adipogenic gene expression.