Keck T, Jargon D, Klünsch A, Thomusch O, Richter S, Friebe V, Adam U, Hopt U T
Department of General and Visceral Surgery, University of Freiburg, Freiburg, Germany.
Pancreatology. 2006;6(4):316-22. doi: 10.1159/000092797. Epub 2006 Apr 20.
The prediction of the course of acute pancreatitis and its arising complications is of clinical importance. The aim of this study was to judge the time course and relevance of matrix metalloproteinase-9 (MMP-9), a PMN-derived protease, for the development of pulmonary complications in two models of acute pancreatitis.
MMP-9 was evaluated in a standardized experimental model of acute pancreatitis. Mild edematous (n = 12) and severe necrotizing pancreatitis (n = 48) were induced by intravenous cerulein or intravenous cerulein and intraductal application of glycodeoxycholic acid and compared to control animals. 1, 6, 9, 12, 24 and 72 h after induction, rats were sacrificed and damage to the lung and the pancreas was quantified by histology and extravasation of Evans blue. At 1, 6, 9, 12, 24 and 72 h, we determined MMP-9 in serum by ELISA.
In our model, MMP-9 in serum was increased in the group with severe acute pancreatitis in comparison to mild edematous pancreatitis and controls at each evaluated time point (p < 0.05). The maximum release of MMP-9 preceded the development of pulmonary complications, verified by histology and extravasation of Evans blue. MMP-9 showed a negative predictive value of 96.2% and a positive predictive value of 100% for the development of pulmonary complications.
MMP-9 in serum allows a valid grouping to severe and mild courses of experimental acute pancreatitis with a good predictive value for the development of pulmonary complications. MMP-9 should be evaluated as a valid single marker for the prediction of progression and the development of pulmonary complications in acute pancreatitis in clinical studies.
急性胰腺炎病程及其并发症的预测具有临床重要性。本研究的目的是在两种急性胰腺炎模型中,判断中性粒细胞衍生的蛋白酶基质金属蛋白酶-9(MMP-9)对于肺部并发症发生发展的时间进程及相关性。
在标准化的急性胰腺炎实验模型中评估MMP-9。通过静脉注射雨蛙素或静脉注射雨蛙素并经导管应用甘氨脱氧胆酸诱导轻度水肿性胰腺炎(n = 12)和重度坏死性胰腺炎(n = 48),并与对照动物进行比较。诱导后1、6、9、12、24和72小时,处死大鼠,通过组织学和伊文思蓝外渗对肺和胰腺的损伤进行定量。在1、6、9、12、24和72小时,我们通过酶联免疫吸附测定法测定血清中的MMP-9。
在我们的模型中,与轻度水肿性胰腺炎组和对照组相比,重度急性胰腺炎组血清中的MMP-9在每个评估时间点均升高(p < 0.05)。MMP-9的最大释放先于肺部并发症的发生,这通过组织学和伊文思蓝外渗得到证实。MMP-9对肺部并发症发生的阴性预测值为96.2%,阳性预测值为100%。
血清中的MMP-9可有效区分实验性急性胰腺炎的重度和轻度病程,对肺部并发症的发生具有良好的预测价值。在临床研究中,MMP-9应作为预测急性胰腺炎进展和肺部并发症发生的有效单一标志物进行评估。