手术切除对于许多原发性和继发性肝肿瘤患者仍然是一种重要的治疗选择。对于一些肿瘤较大的患者，可能需要进行扩大性肝切除(eHx)，这可能导致肝衰竭和死亡。我们构建了部分肝切除(pHx)和扩大性肝切除(eHx)的小鼠模型，并在手术后18、36和72小时取样肝组织。我们采用转录组学和代谢组学分析方法，探究pHx和eHx之间在再生和损伤方面的不同潜在机制。结果显示，与pHx相比，eHx与更严重的肝损伤和较低的生存率相关。转录组学数据显示，在手术后18、36和72小时，与假手术组相比，eHx组中有1842、2129和1277个差异表达基因(DEGs)，而pHx组中有962、1305和732个DEGs。与pHx相比，eHx组的DEGs数量在术后18小时达到最大值230个，并逐渐减少到36小时的87个和72小时的43个。代谢组学分析共鉴定了1399种代谢物，筛选出了48种在eHx和pHx之间产生显著差异的代谢物(DPMs)。DEGs和DPMs的联合分析表明，胆固醇代谢和胰岛素抵抗可能是肝再生和扩大性肝切除后小鼠生存的两个重要途径。我们的结果显示pHx和eHx对小鼠肝脏的转录组和代谢组产生了全局影响，并揭示了胆固醇代谢和胰岛素抵抗途径可能参与了pHx和eHx术后的再生。© 2023. BioMed Central Ltd., part of Springer Nature.

Surgical resection remains a critical treatment option for many patients with primary and secondary hepatic neoplasms. Extended hepatectomy (eHx) may be required for some patients with large tumors, which may cause liver failure and death. Partial hepatectomy (pHx) and eHx mouse models were constructed, liver tissues were sampled at 18, 36, and 72 h posthepatectomy. Transcriptome and metabolome analyses were employed to explore the different potential mechanisms in regeneration and injury between pHx and eHx. The results showed that eHx was associated with more severe liver injury and lower survival rates than pHx. Transcriptomics data showed there were 1842, 2129, and 1277 differentially expressed genes (DEGs) in eHx and 962, 1305, and 732 DEGs in pHx at 18, 36, and 72 h posthepatectomy, respectively, compared with the those in the sham groups. Compared with pHx, the number of DEGs in the eHx group reached a maximum of 230 at 18 h after surgery and decreased sequentially to 87 and 43 at 36 and 72 h. Metabolomics analysis identified a total of 1399 metabolites, and 48 significant differentially produced metabolites (DPMs) were screened between eHx and pHx. Combined analysis of DEGs and DPMs indicated that cholesterol metabolism and insulin resistance may be two important pathways for liver regeneration and mouse survival postextended hepatectomy. Our results showed the global influence of pHx and eHx on the transcriptome and metabolome in mouse liver, and revealed cholesterol metabolism and insulin resistance pathways might be involved in regeneration post-pHx and -eHx.© 2023. BioMed Central Ltd., part of Springer Nature.