Weidenbach H, Lerch M M, Turi S, Bachem M, Adler G
Department of Medicine I, Ulm University, Germany.
Digestion. 1997;58(1):50-7. doi: 10.1159/000201423.
In chronic pancreatitis the exocrine pancreatic tissue is replaced by extracellular matrix deposits from fibroblasts. We have stimulated fibrogenesis in the pancreas by inducing a single episode of cerulein pancreatitis (10 microg/kg/h for 12 h). We have used a spectrophotometrical assay to measure the tissue hydroxyproline content and immunohistochemistry to study the transient deposition of extracellular matrix in the pancreas. We have investigated whether a potent prolyl 4-hydroxylase inhibitor (HOE-077) can influence the deposition of extracellular matrix in the pancreas. Three days after the induction of the pancreatitis we found the maximum increase in pancreatic hydroxyproline content (by 63%), the maximum decrease in total protein content and amylase activity (by -39 and -86%, respectively), as well as a significant increase in DNA content and the deposition of interstitial collagen fibers on electron microscopy. By immunohistochemistry the largest expansion of extracellular matrix components was found for fibronectin. HOE 077, regardless of the concentration administered, failed to affect any of these parameters. We conclude that the induction of a single episode of cerulein pancreatitis and the serial determination of pancreatic hydroxyproline content represents a simple method to induce and monitor experimental fibrogenesis in the pancreas. Prolyl 4-hydroxylase inhibition did not affect the course of extracellular matrix deposition in the pancreas.
在慢性胰腺炎中，胰腺外分泌组织被成纤维细胞产生的细胞外基质沉积物所取代。我们通过诱发单次雨蛙素性胰腺炎（10微克/千克/小时，持续12小时）来刺激胰腺中的纤维生成。我们使用分光光度法测定组织羟脯氨酸含量，并通过免疫组织化学研究胰腺中细胞外基质的短暂沉积。我们研究了一种强效脯氨酰4-羟化酶抑制剂（HOE-077）是否会影响胰腺中细胞外基质的沉积。在诱发胰腺炎三天后，我们发现胰腺羟脯氨酸含量达到最大增幅（增加63%），总蛋白含量和淀粉酶活性降至最低（分别下降39%和86%），同时DNA含量显著增加，电子显微镜下间质胶原纤维沉积增多。通过免疫组织化学发现，纤连蛋白的细胞外基质成分扩张最为明显。无论给予何种浓度的HOE 077，均未能影响上述任何参数。我们得出结论，诱发单次雨蛙素性胰腺炎并连续测定胰腺羟脯氨酸含量是一种在胰腺中诱导和监测实验性纤维生成的简单方法。抑制脯氨酰4-羟化酶并不影响胰腺中细胞外基质沉积的进程。
