Wang Z H, Manabe T, Ohshio G, Hirano T, Okada N, Imamura T, Kawaguchi Y, Yotsumoto F, Yamaki K, Imamura M
First Department of Surgery, Faculty of Medicine, Kyoto University, Japan.
Arzneimittelforschung. 1995 Oct;45(10):1082-6.
The effect of a potent protease inhibitor, sepimostat mesilate (CAS 103926-82-5, FUT-187), on acute interstitial edematous pancreatitis induced by a supramaximal dose of cerulein, a cholecystokinin (CCK) analogue, was evaluated. The serum amylase activity increased 18-fold over normal control after the infusion of cerulein at 5 micrograms/kg/h for 6 h. The serum lipase activity showed a 235-fold increase. An elevated pancreatic water content, pancreatic interstitial edema, inflammatory infiltration and vacuolization of the acinar cells were found. Redistribution of cathepsin B shifted from the lysosomal pellet fraction to the zymogen granule pellet fraction was noted in the early stages. All these parameters of pancreatitis mentioned above were inhibited by FUT-187 pretreatment at doses of 30 to 300 mg/kg. These observations suggest that FUT-187 inhibits the redistribution of cathepsin B shift from the lysosomal fraction to the zymogen fraction in cerulein-induced acute pancreatitis and improves the parameters of acute pancreatitis.
评估了强效蛋白酶抑制剂甲磺酸西莫司他（CAS 103926 - 82 - 5，FUT - 187）对由超最大剂量的胆囊收缩素（CCK）类似物雨蛙素诱导的急性间质性水肿性胰腺炎的影响。以5微克/千克/小时的剂量输注雨蛙素6小时后，血清淀粉酶活性比正常对照增加了18倍。血清脂肪酶活性增加了235倍。发现胰腺含水量升高、胰腺间质水肿、炎性浸润以及腺泡细胞空泡化。在早期阶段注意到组织蛋白酶B从溶酶体沉淀部分重新分布到酶原颗粒沉淀部分。上述胰腺炎的所有这些参数都被30至300毫克/千克剂量的FUT - 187预处理所抑制。这些观察结果表明，FUT - 187抑制雨蛙素诱导的急性胰腺炎中组织蛋白酶B从溶酶体部分向酶原部分的重新分布，并改善急性胰腺炎的参数。
