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肝细胞乳酸化修饰促细胞增殖和部分肝切除术后肝再生

肖荣城 魏灿 韩思远 赵琪 王冉冉 王华 方玲

中国药理学通报2025,Vol.41Issue(8):1445-1453,9.
中国药理学通报2025,Vol.41Issue(8):1445-1453,9.DOI:10.12360/CPB202501020

肝细胞乳酸化修饰促细胞增殖和部分肝切除术后肝再生

Lactylation for hepatocyte proliferation and liver regeneration after hepatectomy

肖荣城 1魏灿 2韩思远 1赵琪 1王冉冉 1王华 3方玲1

作者信息

  • 1. 安徽医科大学药学院||安徽医科大学第一附属医院药剂科||国家中医药管理局中药化学三级实验室,安徽 合肥 230022
  • 2. 合肥市第二人民医院泌尿外科,安徽 合肥 230000
  • 3. 安徽医科大学第一附属医院肿瘤科,安徽 合肥 230022
  • 折叠

摘要

Abstract

Aim To investigate the changes in hepatic lactylation during liver regeneration and its impact on regeneration.Methods A partial hepatectomy(PHx)mouse model was used to study liver regenera-tion.Sodium oxamate was administered intraperitoneal-ly to inhibit lactate dehydrogenase,and blood and liver tissues were collected at different time points post-sur-gery.The histopathological status was observed using HE staining.Proliferating cell nuclear antigen(PC-NA)levels were detected by immunohistochemistry.Lactylation was assessed using immunofluorescence.Liver LDH enzyme activity,lactate levels and serum alanine aminotransferase(ALT)and aspartate trans-aminase(AST)levels were measured using assay kits.Results After PHx,the liver volume of mice gradual-ly increased,returning to preoperative size on day 7.PCNA levels peaked at 48 hours post-surgery.Liver tissue lactate levels increased to approximately 1.5 times the preoperative level at 12 hours post-surgery and remained elevated until day 7.The lactylation lev-el in hepatocytes peaked at 24 hours post-surgery,gradually declined after 48 hours,and returned to pre-operative levels on day 7.Compared to the PHx group,the sodium oxamate(750 mg·kg-1)+PHx group showed significantly reduced lactylation levels in hepa-tocytes and a smaller liver regeneration volume on day 7.Conclusion Lactylation regulates hepatocyte pro-liferation and promotes liver regeneration after PHx.

关键词

肝再生/部分肝切除术/乳酸化修饰/乳酸/草氨酸钠/肝细胞增殖

Key words

liver regeneration/partial hepatectomy/lactylation/lactate/oxamate/hepatocyte proliferation

分类

医药卫生

引用本文复制引用

肖荣城,魏灿,韩思远,赵琪,王冉冉,王华,方玲..肝细胞乳酸化修饰促细胞增殖和部分肝切除术后肝再生[J].中国药理学通报,2025,41(8):1445-1453,9.

基金项目

国家自然科学基金资助项目(No 81600498) (No 81600498)

安徽省教育厅高等学校科学研究重点项目(No 2022AH051163) (No 2022AH051163)

中国药理学通报

OA北大核心

1001-1978

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