应用代谢组学方法研究重症急性胰腺炎继发MOF的早期预警机制

Severe acute pancreatitis (SAP) complicated with multiple organ failure (MOF) lead to a common cause of death in patients. Early prediction and early intervention is still the key clinical issues. It confirmed that prognosis is associated with the evaluation system of SAP. But it is based on that the "severe" has occurred and obvious lag was present. In animal experiments, our study have found that as early as before the change of major organ function in rats with severe acute pancreatitis, the metabolic spectrum has occurred a significant change. The abnormal metabolites peaks were showed in the loading diagram and total ion current diagram reveals that SAP rats were divided into both groups related to prognosis (survival and death) . This results suggest that early detection of SAP metabolic spectrum can predict prognosis as well as the severity of the disease. Therefore, this study was to establish an early,rapid and efficient metabonomic approach for prognostic evaluation of SAP complicated with MOF and explore some potential biomarkers related with patient’outcome using NMR and HPLC/MS spectroscopy analytical techniques.

重症急性胰腺炎（SAP）并发多脏器功能衰竭（MOF）是导致患者死亡的常见原因，如何实现早期预警并针对其中的关键环节进行干预是临床诊治的热点问题。目前证实针对SAP的评价体系与预后具有有一定的相关性，但都是建立在“重症”已发生的基础上，存在明显滞后性；本研究在动物实验中发现，早在大鼠重症急性胰腺炎主要脏器功能（呼吸功能及肝肾功能）发生改变之前，其代谢谱已发生了显著改变，载荷图显示出现了异常的代谢产物谱峰，总离子流图上显示重度胰腺炎大鼠分成了与预后（生存与死亡）明显相关的两个组；这个结果提示或可以通过检测重症胰腺炎早期的代谢谱来预测疾病的严重程度及预后。基于以上，本实验拟应用NMR技术和LC-MS技术通过主成分分析和多元统计分析的方法构建临床上一个能早期、快速、有效预测重症急性胰腺炎并发多脏器功能衰竭的判别模式，并评价该预测模式的特异性与敏感性，以期为重症急性胰腺炎的预后判断提供一种新方法。

重症急性胰腺炎（SAP）并发多脏器功能衰竭（MOF）是导致患者死亡的常见原因，实现早期预警并针对其中的关键环节进行干预是临床诊治的热点问题。本课题在前期工作基础上，重点收集了轻度急性胰腺炎、中度急性胰腺炎与重度急性胰腺炎患者的血清样本，检测了不同类型急性胰腺炎的代谢网络图谱。通过主成分分析、偏最小二乘法等方法建立区分了轻度急性胰腺炎和中度急性胰腺炎的代谢特征，并区分了重症胰腺炎是否并发MOF的判别模式。进一步采用了多元统计分析方法筛选早期特征性的生物标记物，并对得到的差异生物标记物进行了指认和结构鉴定。本课题的完成为深入认识急性胰腺炎的发病机制和判别预后提供了新的试验资料。