大鼠肝再生启动阶段能量代谢物靶向定量分析

目的 探讨大鼠肝再生 (LR)启动阶段能量代谢物的变化对LR的调控作用。 方法 大鼠随机分为3组，每组5只，包括两个部分肝切除组（PH）和1个正常对照组。运用质谱选择反应检测扫描/多反应检测扫描（SRM/MRM）对29种能量代谢物的含量进行靶向代谢组学鉴定。运用Ingenuity Pathway Analysis (IPA)软件进行整合分析，包括经典途径和分子相互作用网络。 结果 3-磷酸-D-甘油酸酯、一磷酸腺苷、环腺苷酸、D-果糖1,6-二磷酸、磷酸二羟丙酮、单磷酸鸟苷、三磷酸鸟苷、烟酰胺腺嘌呤二核苷酸和烟酰胺腺嘌呤二核苷酸磷酸含量显著增加。α-酮戊二酸、β-D-果糖6-磷酸、枸橼酸、D-葡萄糖-6-磷酸、乳酸、还原型辅酶Ⅱ、草酰乙酸和丙酮酸含量显著减少。聚类分析发现，这些代谢物可以聚为4类。IPA分析表明，肝再生起始阶段的生物分子变化主要与碳水化合物代谢，细胞生长和增殖，机体发育相关。在肝再生启动阶段，磷酸化腺苷酸活化蛋白激酶（AMPK）、缺氧诱导因子1α（HIF-1α）、过氧化物酶体增殖物激活受体（PPAR）、蛋白激酶A（PKA）和磷脂酰肌醇-3激酶/蛋白激酶B（PI3K/Akt）信号通路与能量代谢相关，糖酵解可能是主要的供能方式。 结论 大鼠肝再生启动阶段能量代谢物的变化对肝再生具有调控作用。

Targeted quantitative analysis of energy metabolites in the priming phase during rat liver regeneration

Objective To investigate the regulation of liver regeneration (LR) by changes in energy metabolites in the initiation phase during rat liver regeneration. Methods Rats were randomly divided into 3 groups with 5 rats in each group, including two partial hepatectomy (PH) groups and one normal control group. Selective reaction monitoring/multiple reaction monitoring (SRM/MRM) was employed in the targeted metabolomics identification of 29 energy metabolites. Ingenuity Pathway Analysis (IPA) was applied for integration analysis, including canonical pathway and molecular interaction network. Results The levels of 3-phospho-D-glycerate, AMP, cyclic AMP, D-fructose 1, 6-bisphosphate, dihydroxyacetome phosphate(DHAP), guanosine monophosphate(GMP), guanosine triphosphate(GTP), nicotinamide adenine dinucleotide(NAD) and nicotinamide adenine dinueleotide phosphate(NADP) significantly increased. The levels of alpha-ketoglutarate, beta-D-fructose 6-phosphate, cis-aconitate, D-glucose 6-phosphate, lactate, NADPH, oxaloacetate and pyruvate dramatically reduced. Through hierarchical clustering analysis of energy metabolisms, these energy metabolisms can be grouped into four clusters. IPA showed that the biomolecular changes in the priming phase of liver regeneration are mainly related to carbohydrate metabolism, cellular growth and proliferation, and organismal development. During the priming phase of liver regeneration, adenosine 5’-monphosphate-activated protein kinase (AMPK), hypoxia-inducible factor 1α (HIF-1α), peroxisome proliferator-activated receptor (PPAR), protein kinase A (PKA) and phosphatid linositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathways are involved in energy metabolism, and glycolysis may be the main mode of energy supply. Conclusion The result suggests that the changes of energy matabolites during the initial stage of LR play a regulatory role in live regeneration.