研究对象:大鼠 分析检测平台:GC-TOF/MS(BIOTREE) 期刊:Liver international 影响因子:4.85 发表时间:2015
摘要: Background & Aims: Insufficient liver regeneration and hepatocyte injury caused by excessive portal perfusion are considered to be responsible for post-hepatectomy liver failure (PLF) or small-for-size syndrome in living- donor liver transplantation. Somatostatin can decrease portal vein pressure (PVP) but simultaneously inhibits liver regeneration. This interesting para- dox motivated us to investigate the outcome of PLF in response to somatostatin treatment. Methods: Rats receiving extended partial hepatectomy (90% PH) were treated with octreotide, a somatostatin analogue, or placebo. Animal survival, serum parameters and hepatic histology were evaluated. Metabolomic analysis was performed to investigate the effect of octreotide on hepatocyte metabolism. Results: Despite significantly inhibiting early regeneration, octreotide application noticeably improved the hepatic histology, liver function and survival after PH but did not decrease the PVP level. Metabolomic analysis exhibited that octreotide profoundly and exclusively altered the levels of five metabolites that participate in or closely associate with the methionine cycle, a biochemical reaction that uniquely produces S-adenosylmethionine (SAMe), an active methyl residual donor for methyl- transferase reactions. Among these metabolites, methylthioadenosine (MTA), a derivate of SAMe, increased three-fold and was found independently improve the hepatic histology and reduce inflammatory cytokines in hepatectomized rats. Conclusions: Octreotide exclusively regulates the methionine cycle reaction and augments the MTA level in hepatocytes. MTA prominently protects hepatocytes against shear stress injury and reduces the secondary inflammation, thereby protecting rats from PLF.
药物代谢组学案例分析药理研究:奥曲肽的肝脏保护作用研究对象:大鼠分析检测平台:GC-TOF/MS(BIOTREE)期刊:Liver international影响因子:4.85发表时间:2015摘要:Background & Aims: Insufficient liver regeneration and hepatocyte injury caused by excessive portal perfusion are considered to be