Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chu-o-ku, Kobe, Hyogo 650-0017, Japan.
Arch Biochem Biophys. 2012 Jun 15;522(2):107-20. doi: 10.1016/j.abb.2012.03.025. Epub 2012 Mar 29.
Novel and effective drugs against acute pancreatitis are required. Therefore, we examined the changes in the metabolite levels in the serum and pancreatic tissue of mice with cerulein- and arginine-induced pancreatitis using gas-chromatography/mass-spectrometry (GC/MS) and investigated whether these alterations affected the severity of acute pancreatitis. In the cerulein-induced pancreatitis model, 93 and 129 metabolites were detected in the serum and pancreatic tissue, respectively. In the L-arginine-induced acute pancreatitis model, 120 and 133 metabolites were detected in the serum and pancreatic tissue, respectively. Among the metabolites, the concentrations of tricarboxylic acid (TCA) cycle intermediates and amino acids were altered in pancreatitis, and in pancreatic tissue, the levels of the intermediates involved in the initial part of the TCA cycle were increased and those of the intermediates involved in the latter part of the TCA cycle were decreased. Some metabolites exhibited similar changes in both pancreatitis mouse models, e.g., the levels of glutamic acid and O-phosphoethanolamine were significantly decreased in the pancreatic tissue. Supplementation with glutamic acid and O-phosphoethanolamine attenuated the severity of cerulein-induced acute pancreatitis. Our results suggest that GC/MS-based metabolomics is capable of accurately representing the status of acute pancreatitis, leading to the discovery of therapeutic agents for pancreatitis.
需要寻找新型有效的急性胰腺炎治疗药物。因此，我们采用气相色谱/质谱联用（GC/MS）方法检测了鹅膏蕈碱和精氨酸诱导的胰腺炎小鼠血清和胰腺组织中代谢物水平的变化，并探讨了这些变化是否影响急性胰腺炎的严重程度。在鹅膏蕈碱诱导的胰腺炎模型中，分别在血清和胰腺组织中检测到 93 种和 129 种代谢物。在精氨酸诱导的急性胰腺炎模型中，分别在血清和胰腺组织中检测到 120 种和 133 种代谢物。在这些代谢物中，三羧酸（TCA）循环中间产物和氨基酸的浓度在胰腺炎中发生改变，在胰腺组织中，TCA 循环起始部分的中间产物水平升高，而 TCA 循环后半部分的中间产物水平降低。一些代谢物在两种胰腺炎小鼠模型中表现出相似的变化，例如，胰腺组织中谷氨酸和 O-磷酸乙醇胺的水平显著降低。补充谷氨酸和 O-磷酸乙醇胺可减轻鹅膏蕈碱诱导的急性胰腺炎的严重程度。我们的研究结果表明，基于 GC/MS 的代谢组学能够准确反映急性胰腺炎的状态，从而发现治疗胰腺炎的药物。
