药物代谢组学案例分析

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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 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.

Keywords: hepatectomy liver failure (PLF)、portal vein pressure (PVP)、methylthioadenosine (MTA)

研究背景：

哮喘常由呼吸道炎症导致，但目前诊疗中还缺乏简便易行的呼吸道炎症快速判定措施。来源于尿液、血液和呼出气冷凝液的代谢物可用于疾病的分型和诊断，代谢组学技术通过检测分析上述样本的代谢物指纹图谱可获得与疾病相关的最重要的代谢物和代谢途径。针对这些特异性较强的生物标志物可进一步建立快速检测方法，用于类似哮喘等复杂疾病的分型和早期诊断。本研究尝试通过GC-TOF/MS方法分析哮喘病人血样，从而获得可能用于早期诊断的潜力生物标志物。