Leonhardt U, Seidensticker F, Stöckmann F, Creutzfeldt W
Zentrum Innere Medizin, Abteilung Gastroenterologie und Endokrinologie, Göttingen, Germany.
Pancreas. 1993 Jan;8(1):98-102. doi: 10.1097/00006676-199301000-00017.
The present study investigates the effect of oral pretreatment with the protease inhibitor camostate on the outcome of pancreatitis in three experimental models. In pancreatitis induced by overstimulation with cholecystokinin (CCK) in rats, pancreatic enzymes and the histological degree of pancreatitis were quantified; in pancreatitis induced by a choline-deficient ethionine-supplemented (CDE) diet in mice, the effect on survival was monitored; and in bile-induced pancreatitis in rats, the effect on survival, pancreatic enzymes, and histology was studied. Feeding of camostate (200 mg/kg/day) for 2 weeks worsened the histological degree of pancreatitis induced by overstimulation with CCK or by injection of taurocholate. The concentration of amylase in the pancreas and in serum was significantly lower after pretreatment with camostate, both in cerulein-induced pancreatitis and in bile-induced pancreatitis, while the concentration of trypsin in the pancreas was significantly increased in the camostate-treated animals. Pretreatment with camostate significantly lowered survival. In pancreatitis induced by a CDE diet, 3 of 20 mice survived the observation period, while 9 of 20 control animals survived (p < 0.05). In taurocholate-induced pancreatitis, 5 of 29 rats were alive after 3 days versus 18 of 30 animals in the control group (p < 0.001). CCK levels were not elevated in camostate-treated rats, when pancreatitis was induced 24 h after finishing camostate feeding. It is concluded that camostate induced pancreatic hypertrophy and increased concentration of proteolytic enzymes aggravate experimental panceatitis and that this is not mediated by increased CCK levels.
本研究在三种实验模型中探讨了口服蛋白酶抑制剂卡莫司他预处理对胰腺炎结局的影响。在大鼠胆囊收缩素（CCK）过度刺激诱导的胰腺炎中，对胰腺酶和胰腺炎的组织学程度进行了量化；在小鼠胆碱缺乏乙硫氨酸补充（CDE）饮食诱导的胰腺炎中，监测了对生存的影响；在大鼠胆汁诱导的胰腺炎中，研究了对生存、胰腺酶和组织学的影响。给予卡莫司他（200mg/kg/天）2周会使CCK过度刺激或注射牛磺胆酸盐诱导的胰腺炎的组织学程度恶化。在蛙皮素诱导的胰腺炎和胆汁诱导的胰腺炎中，用卡莫司他预处理后，胰腺和血清中的淀粉酶浓度均显著降低，而在接受卡莫司他治疗的动物中，胰腺中的胰蛋白酶浓度显著升高。用卡莫司他预处理显著降低了生存率。在CDE饮食诱导的胰腺炎中，20只小鼠中有3只在观察期内存活，而20只对照动物中有9只存活（p<0.05）。在牛磺胆酸盐诱导的胰腺炎中，3天后29只大鼠中有5只存活，而对照组30只动物中有18只存活（p<0.001）。在停止给予卡莫司他喂养24小时后诱导胰腺炎时，卡莫司他治疗的大鼠CCK水平未升高。结论是，卡莫司他诱导的胰腺肥大和蛋白水解酶浓度增加会加重实验性胰腺炎，且这不是由CCK水平升高介导的。
