Protective Effect of a Pancreatic Elastase Inhibitor Against a Variety of Acute Pancreatitis in Rats

The Japanese Journal of Pharmacology

Keiji Miyata¹  Mayumi Yamano¹  Toshimitsu Yamada¹ 

[1] Pharmacology Laboratories, Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd.

关键词: Acute pancreatitis;    Pancreatic elastase;    Closed duodenal loop;    Cerulein;    Taurocholate;   

DOI  :  10.1254/jjp.77.193

学科分类：药理学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(27)Cited-By(5)Protective effect of trifluoroacetyl-L-lysyl-L-alaninanilide hydrochloride (compound 1), a pancreatic elastase inhibitor, on three types of acute pancreatitis models was examined in rats. Mild, moderate and severe acute pancreatitis were induced by cerulein, the closed duodenal loop method and retrograde injection of a taurocholate plus trypsin solution into the pancreatic duct, respectively. Intravenous infusion of compound 1 at a dose of 30 mg/kg/hr resulted in lower increases in serum amylase, lipase, blood urea nitrogen (BUN) and creatinine levels in rats with mild cerulein-induced edematous pancreatitis. Compound 1 had no beneficial effect on pancreatitis in rats with moderate pancreatitis. In rats with severe pancreatitis, prophylactic treatment of compound 1 (30 mg/kg/hr) reduced both elevated serum BUN level and ascitic volume, and it histologically inhibited the extent of pancreatic edema and hemorrhage. These results suggest that pancreatic elastase is partially responsible for pancreatic edema and hemorrhage exhibited by rats with severe acute pancreatitis.

【 授权许可】

Unknown