Lempinen Marko, Stenman Ulf-Håkan, Halttunen Jorma, Puolakkainen Pauli, Haapiainen Reijo, Kemppainen Esko
Second Department of Surgery, Helsinki University Central Hospital, Helsinki, Finland.
Pancreatology. 2005;5(2-3):157-64. doi: 10.1159/000085267. Epub 2005 Apr 21.
BACKGROUND/AIMS: Trypsinogen activation is thought to play a crucial role in the pathogenesis of acute pancreatitis (AP). Our aim was to characterize the very early sequential changes of trypsinogen-1, trypsinogen-2, the trypsin-2-alpha1-antitrypsin complex (T2-AAT), and pancreatic secretory trypsin inhibitor (PSTI) in serum from patients with pancreatitis induced by endoscopic retrograde cholangiopancreatography (ERCP), a model for studying the early phase of the disease in humans.
The study population consisted of 659 consecutive patients with 897 ERCP procedures. Blood samples were obtained before and at different time points after the procedure. The serum concentrations of trypsinogen-1 and trypsinogen-2, PSTI and T2-AAT were determined by time-resolved immunofluorometric assays.
ERCP-induced pancreatitis developed after 50 of the 897 ERCP procedures (5.6%). Sixty-one randomly selected ERCP patients without post-ERCP pancreatitis served as controls. Trypsinogen-1 and trypsinogen-2 showed an equally steep increase during the two first hours after ERCP in patients developing AP, but trypsinogen-1 decreased more rapidly than trypsinogen-2, which remained elevated during the 5-day study period. Serum PSTI also increased rapidly whereas T2-AAT increased more slowly peaking at 24 h. In patients developing post-ERCP pancreatitis the median concentration of trypsinogen-1 was markedly higher than in the controls already before the ERCP procedure. In the control group the concentrations of trypsinogen-1, trypsinogen-2, PSTI and T2-AAT did not change significantly.
The rapid increase of trypsinogen-1 and trypsinogen-2 and PSTI in the early phase of AP suggests that release of pancreatic enzymes is the initial event while the delayed increase of T2-AAT may reflect that the capacity of the intrapancreatic PSTI-based inhibitory mechanism has been exhausted.
背景/目的：胰蛋白酶原激活被认为在急性胰腺炎（AP）的发病机制中起关键作用。我们的目的是描述内镜逆行胰胆管造影术（ERCP）诱发胰腺炎患者血清中胰蛋白酶原-1、胰蛋白酶原-2、胰蛋白酶-2-α1抗胰蛋白酶复合物（T2-AAT）和胰腺分泌性胰蛋白酶抑制剂（PSTI）在疾病极早期的连续变化情况，ERCP是研究人类疾病早期阶段的一个模型。
研究人群包括连续接受897次ERCP手术的659例患者。在手术前及术后不同时间点采集血样。通过时间分辨免疫荧光分析法测定血清中胰蛋白酶原-1、胰蛋白酶原-2、PSTI和T2-AAT的浓度。
897次ERCP手术中有50次（5.6%）发生了ERCP诱发的胰腺炎。随机选取61例无ERCP术后胰腺炎的ERCP患者作为对照。发生AP的患者在ERCP后的最初两小时内，胰蛋白酶原-1和胰蛋白酶原-2均呈现同样急剧的升高，但胰蛋白酶原-1下降速度比胰蛋白酶原-2更快，后者在为期5天的研究期间一直保持升高。血清PSTI也迅速升高，而T2-AAT升高较慢，在24小时达到峰值。发生ERCP术后胰腺炎的患者中，胰蛋白酶原-1的中位浓度在ERCP手术前就明显高于对照组。在对照组中，胰蛋白酶原-1、胰蛋白酶原-2、PSTI和T2-AAT的浓度没有显著变化。
AP早期胰蛋白酶原-1、胰蛋白酶原-2和PSTI的快速升高表明胰腺酶的释放是初始事件，而T2-AAT的延迟升高可能反映基于胰腺内PSTI的抑制机制的能力已被耗尽。
