Geokas M C, Largman C, Durie P R, Brodrick J W, Ray S B, O'Rourke M, Vollmer J
Am J Pathol. 1981 Oct;105(1):31-9.
A canine model of bile-induced pancreatitis has been employed to investigate time-dependent changes in the molecular forms of trypsin in blood and ascitic fluid in this disease. The distribution of immunoreactive trypsin as trypsinogen and trypsin bound to plasma inhibitors in ascitic fluid and plasma during the course of the disease has been investigated by means of a radioimmunoassay for canine pancreatic cationic trypsin. In addition, trypsinlike amidase activity was determined in plasma and ascitic fluid using Z-Gly-Gly-Arg-beta-Nap as substrate. Early plasma and ascitic fluid samples in four dogs that died contained primarily trypsinogen, while extensive activation of trypsinogen to alpha 2-macroglobulin and alpha 1-protease inhibitor-bound trypsin occurred in the course of the disease. A fifth dog survived and showed little activation of trypsinogen. In the four dogs that died, the levels of trypsinlike amidase activity in the ascitic fluid were substantial throughout the course of the disease. The plasma levels of trypsinlike activity in these animals were much lower, but increased during the disease process. The dog that survived had lower concentrations of trypsinlike activity in ascitic fluid and plasma. These results suggest that activation of trypsinogen resulting in inhibitor-bound forms of trypsin in ascitic fluid and plasma is important in the pathogenesis of acute pancreatitis.
采用胆汁诱导的犬胰腺炎模型来研究该疾病中血液和腹水中胰蛋白酶分子形式的时间依赖性变化。通过犬胰阳离子胰蛋白酶放射免疫分析法，研究了疾病过程中腹水和血浆中作为胰蛋白酶原的免疫反应性胰蛋白酶以及与血浆抑制剂结合的胰蛋白酶的分布情况。此外，以Z-甘氨酰-甘氨酰-精氨酸-β-萘胺为底物，测定了血浆和腹水中类胰蛋白酶酰胺酶活性。四只死亡犬的早期血浆和腹水样本主要含有胰蛋白酶原，而在疾病过程中胰蛋白酶原大量激活为与α2-巨球蛋白和α1-蛋白酶抑制剂结合的胰蛋白酶。第五只犬存活下来，胰蛋白酶原激活很少。在四只死亡犬中，腹水中类胰蛋白酶酰胺酶活性在疾病全过程中都很高。这些动物血浆中的类胰蛋白酶活性水平低得多，但在疾病过程中有所增加。存活犬的腹水和血浆中类胰蛋白酶活性浓度较低。这些结果表明，胰蛋白酶原激活导致腹水和血浆中出现与抑制剂结合形式的胰蛋白酶，在急性胰腺炎发病机制中起重要作用。
