Funakoshi A, Miyasaka K, Jimi A, Kitani K, Teraoka H, Yoshida N
National Kyushu Cancer Center, Fukuoka, Japan.
Digestion. 1992;52(3-4):145-51. doi: 10.1159/000200946.
We examined the protective effect of human pancreatic secretory trypsin inhibitor (PSTI), a specific trypsin inhibitor secreted from pancreatic acinar cells into the pancreatic duct, on cerulein-induced acute pancreatitis in conscious rats. The protective effect of human PSTI-RS, an analogue of PSTI with Arg-44 to Ser substitution which has a longer half-life in vitro, was also examined. Intraperitoneal administration of a pharmacological dose of cerulein to conscious rats induced acute pancreatitis, characterized by light microscopy as cellular disorganization of the acini and interstitial edema. Intravenous infusion of human PSTI (10, 50 or 250 micrograms/rat/h) into rats with cerulein-induced acute pancreatitis decreased their pancreatic wet weight and plasma amylase concentration. It also caused a dose-dependent decrease in vacuoles in acinar cells and interstitial edema. Human PSTI-RS, which has a longer half-life in vivo, was more effective than native PSTI at the same dose rate (10 micrograms/rat/h) in reducing pancreatitis. These results suggest that human PSTI may have a beneficial effect on acute pancreatitis.
我们研究了人胰腺分泌性胰蛋白酶抑制剂(PSTI),一种从胰腺腺泡细胞分泌到胰管中的特异性胰蛋白酶抑制剂,对清醒大鼠中蛙皮素诱导的急性胰腺炎的保护作用。我们还研究了人PSTI-RS的保护作用,它是PSTI的类似物,其第44位氨基酸由精氨酸替换为丝氨酸,在体外具有更长的半衰期。向清醒大鼠腹腔注射药理剂量的蛙皮素可诱发急性胰腺炎,光镜下表现为腺泡细胞结构紊乱和间质水肿。向患有蛙皮素诱导的急性胰腺炎的大鼠静脉输注人PSTI(10、50或250微克/大鼠/小时)可降低其胰腺湿重和血浆淀粉酶浓度。它还导致腺泡细胞中的空泡和间质水肿呈剂量依赖性减少。在相同剂量率(10微克/大鼠/小时)下,在体内具有更长半衰期的人PSTI-RS在减轻胰腺炎方面比天然PSTI更有效。这些结果表明,人PSTI可能对急性胰腺炎具有有益作用。