Disturbances of extracellular protein metabolism in ceruleininduced pancreatitis

Abstract

Chronic pancreatitis (CP) is still a serious clinical problem due to the significant difficulties in its diagnosis, especially in the initial stages of development. Among the mechanisms that mediate the pathogenesis of CP and lead to pancreatitis-related disorders is unregulated activation of proteolytic enzymes, namely, matrix metalloproteinases (MMPs). The aim of our study was to determine the disturbances of protein metabolism under the conditions of CP alone or in combination with diabetes type 1 (CP+DT1). Herein, CP was induced in the nonlinear male rats by intraperitoneal injection of cerulein (5 μg·kg-1 of body weight; five times during fives day). DT1 was modeled in the rats with CP by a single intraperitoneal injection of streptozotocin (65 mg·kg-1 of the body weight). The levels of MMP-2 and-9 were determined by enzyme-linked immune sorbent assay, and the level of low and middle molecular weight (LMMW) substance was measured spectrophotometrically, while the peptide fractions were analyzed by size exclusion chromatography. The present study revealed a significant increase of MMP-2 and MMP-9 levels in the serum, liver and pancreas of the rats with CP and CP+DT1. Elevated levels of MMPS may act as a factor for the initiation of subsequent cascade of events resulting in the development of pancreatitis-associated complications. Pathogenesis of chronic pancreatitis alone or in combination with diabetes type 1 has been accompanied by the formation and accumulation of LMMW substance, changes in peptide composition and level of individual peptides in the tissues of the rats. Such alterations are among key triggers of amplification of metabolic disorders under chronic pancreatitis.