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
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)