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EXPERIMENTAL ACUTE PANCREATITIS INDUCED BY EXCESSIVE DOSES OF CAERULEIN IN RATS : PROTECTIVE AND THERAPEUTIC EFFECTS OF TRYPSIN INHIBITOR URINASTATIN AND CCK RECEPTOR ANTAGONIST CR1392

English (英語)

The Kobe journal of the medical sciences

34(2)

93-112

1988-04

First, a new experimental model of acute pancreatitis was produced in rats by subcutaneous injections of supramaximal doses of caerulein, a synthetic analogue of cholecystokinin (CCK). Four subcutaneous injections of 20 μg/kg body weight of caerulein markedly increased of serum amylase, lipase, and anionic trypsin(ogen) levels, which peaked at 4-6 hr after the first caerulein injection. Remarkable interstitial edema of the pancreas and various numbers and sizes of cytoplasmic vacuoles in acinar cells were seen at the early time points (4-6 hr), and cellular infiltration at later periods (9-12 hr). These light microscopic findings almost completely disappeared after 24 hr. The electron microscopic examination, however, revealed that vacuoles and destructive changes in the cytoplasmic organelles in acinar cells were still detectable even after 24 hr and these structural alterations disappeared after 7 days. Secondly, we examined the therapeutic and protective effects of urinary trypsin inhibitor, urinastatin, and of the CCK receptor antagonist, CR1392, on caerulein-induced acute pancreatitis. Five intraperitoneal injections of 50,000 U/kg body weight urinastatin inhibited the increase of serum amylase activity and lessened histologic evidence of interstitial edema, vacuolization, and inflammation. Pretreatment with CR1392 abolished the elevation of serum amylase activity and completely alleviated the histologic alterations. CR1392, even when given after the induction of acute pancreatitis (post-treatment), reduced the increase of serum amylase activity and the degree of cytoplasmic vacuolization.

cholecystokinin (CCK)-receptor antagonist

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